Polymerization process and materials for biomedical applications

ABSTRACT

A molded component or article for biomedical use is prepared from a crosslinkable non-water-soluble polymer which when crosslinked and saturated with water forms a hydrogel. The polymer is formulated as a composition containing a non-aqueous diluent in addition to the polymer, the diluent being present in a volumetric proportion that is substantially equal to the volumetric proportion of water in the hydrogel that would be formed when the polymer is crosslinked and saturated with water. The composition is cast in a mold where the composition is exposed to conditions that cause crosslinking to occur by a reaction to which the non-aqueous diluent is inert. The crosslinking reaction produces a molded non-aqueous gel which is then converted to a hydrogel by substituting an aqueous liquid such as water or physiological saline for the non-aqueous diluent. The use of a molding composition whose curing consists essentially entirely of crosslinking results in a molding process that entails little or no shrinkage, and dimensional integrity is maintained up through the formation of the hydrogel by using the non-aqueous diluent in essentially the same volumetric proportion as water in the hydrogel.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefits of co-pending U.S. provisionalpatent applications No. 60/357,578, filed on Feb. 15, 2002, and60/366,828, filed on Mar. 22, 2002, for all purposes legally capable ofbeing served thereby. The contents of each of these provisional patentapplications are incorporated herein by reference in their entirety, asare all other patent and literature references cited throughout thisspecification.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a polymerization process for theproduction of polymeric moldings, such as medical device moldings andoptical lenses, preferably contact lenses, intraocular lenses, andophthalmic lenses, in which crosslinkable polymeric precursor mixturesare synthesized and molded. The invention also relates to the novelcrosslinkable polymeric precursor mixtures and moldings obtainable inaccordance with that process.

2. Description of the Prior Art

Polymeric materials have been widely used in biomedical applicationssuch as contact lenses, intraocular lenses, and ophthalmic lenses.Examples of other polymeric biomedical moldings are bandages or woundclosure devices, heart valves, coronary stents, artificial tissues andorgans, and films and membranes. The advantage of polymeric materials isthat a large number of materials are available to obtain desiredmechanical, physical, chemical, and optical properties of products byselecting the components and compositions of materials. The propertiesof polymeric materials also depend on their morphologies which can bemanipulated by adjusting the processing conditions such as mixing.

In biomedical applications of polymeric materials, major concerns arebiocompatibility and toxicity. Consequently, all biomedical devices arerequired to meet the stringent regulations administered by the US Food &Drug Administration (FDA). Concerns of biocompatibility and toxicityaffect the selection of materials as well as the process design.

In order to ensure biocompatibilty and safety, a common practice is toemploy a post-production treatment on polymeric materials for biomedicalapplications. For entities made from direct polymerization of liquidmonomers (i.e., monomer-based casting system), tedious extractiontreatment is often required, in which a biomedical product or device isimmersed in water or other non-toxic liquid for a prolonged period,often hours at elevated temperatures. During the extraction process,residual monomers, catalysts, and other harmful species are removed bydiffusion which proceeds slowly. Upon completing an extraction step, thetreated polymeric part is essentially free of toxic ingredients and canbe used safely for a biomedical use. Thus, in the production ofpolymeric materials for biomedical applications, the monomer-basedcasting system is costly because it requires additional equipment, timeand labor for the postproduction extraction step which increases thecost and reduces the efficiency of production significantly.

For the production of precision parts such as contact lenses,intraocular lenses, and ophthalmic lenses, another drawback of amonomer-based casting system is that the shape of the cured articleoften fails to replicate precisely the geometry of the mold cavitybecause of the shrinkage realized upon curing monomers.

When the shrinkage is the major concern of moldings, polymeric productsmay also be produced from polymer resins by injection molding,compression molding, or other techniques well-known and commonlypracticed in the art. However, these techniques require high processingtemperatures and are not suitable for processing thermally sensitivepolymers such as the high-refractive index polymers useful forophthalmic lenses.

Thus, it would be desirable to have an efficient means by whichpolymeric products for biomedical applications could be produced withoutcostly purification, undue shrinkage, or exposing polymers to harshprocessing conditions.

SUMMARY OF THE INVENTION

The present invention is aimed at alleviating or reducing theabove-stated problems. The invention relates to a process for theproduction of moldings, in particular medical device moldings, moreparticularly optical lens moldings which exhibit low shrinkage upon curecompared to curable liquid formulations known in the art and/or do notrequire extraction steps prior to their intended use. Preferred moldingsare contact lenses, intraocular lenses, and ophthalmic lenses. Examplesof other applicable moldings are biomedical moldings such as bandages orwound closure devices, heart valves, coronary stents, artificial tissuesand organs, and films and membranes.

Shrinkage of the polymer during the molding stage is reduced oreliminated in accordance with this invention by using a moldingcomposition that includes a preformed non-water-soluble polymer that iscapable of crosslinking, instead of a monomer. The composition alsocontains a non-aqueous diluent that is inert to the crosslinkingreaction. The volumetric proportion of non-aqueous diluent in themolding composition is derived from the known characteristics that thepolymer will exhibit after the polymer has been crosslinked andsaturated with water. Specifically, the polymer, once crosslinked andsaturated with water or an aqueous liquid such as physiological salineforms a hydrogel that contains a known volumetric proportion of waterdetermined by the molecular characteristics of the crosslinked polymeritself, and that volumetric proportion is used as the volumetricproportion of the non-aqueous diluent in the molding composition withthe not yet crosslinked polymer. Crosslinking of the molding compositionduring the molding stage then produces a non-aqueous gel which in asucceeding step is replaced by an aqueous liquid to form the hydrogel,the volumetric proportion of water in the hydrogel being substantiallythe same as the volumetric proportion of non-aqueous diluent in thecomposition that is placed in the mold. The result is a substantiallyisometric exchange of water or aqueous liquid for the non-aqueousdiluent. The term “aqueous liquid” is used herein to denote either wateror an aqueous solution, particularly a dilute aqueous solution such asphysiological saline.

The term “substantially equal” as used herein in connection with thevolumetric proportions of non-aqueous diluent and water denotes that asmall difference between the volumetric proportions and hence a smallvolume change upon the substitution of the aqueous liquid for thenon-aqueous diluent may occur and is still within the scope of theinvention. The only limitation is that any such change be withintolerance limits established by the industry in which the product ismanufactured and sold and by any regulatory limits that apply to theproduct. Thus, for contact lenses, for example, any deviation betweenthe volume of the non-aqueous gel and the hydrogel that is within theindustry-accepted tolerance limits for contact lenses is acceptable.Such tolerance limits are known among those skilled in the art for eachtype of molded product in addition to being readily determinable fromliterature published by the appropriate regulatory agencies.

The process makes use of a polymeric precursor mixture synthesized atlow temperatures that is shaped into a desired geometry and cured.Preferably, shaping is carried out by placing the precursor mixturebetween two mold halves, after which it is cured and released from themold to produce the moldings of interest. Other aspects of the inventionrelate to the polymeric precursor mixtures obtainable in accordance withthe process of this invention, as well as to the moldings so produced.These aspects of the invention and several presently preferredembodiments will be described in more detail below.

More particularly, the invention in one aspect is directed to a novelcrosslinkable polymeric precursor mixture that comprises a prepolymercontaining crosslinkable groups, which prepolymer is obtained accordingto the present invention. The precursor mixture may optionally containdead polymers, non-reactive diluents, and/or reactive plasticizers.

In another aspect, the invention relates to a novel process in which acrosslinkable polymeric precursor material is constituted, shaped into adesired geometry as a composition containing the polymer and anon-aqueous diluent, preferably by taking on the dimensions defined bythe cavity between two or more mold portions, cured by a source ofpolymerizing energy, released from the mold, and immersed in an aqueousliquid such as water or physiological saline to substitute that liquidfor the non-aqueous diluent, to produce the moldings of interest.

In a further aspect, the invention is directed to a method for preparinga molding which comprises the steps of, first, obtaining a precursormixture containing a crosslinkable prepolymer. The crosslinkableprepolymer is obtained, according to the present invention, by theprocess of 1) mixing together i) one or more different types ofmonomers, ii) optionally, one or more non-reactive diluents, and iii)optionally, a solvent; 2) polymerizing the monomers to give a polymer;3) adding one or more different types of functionalizing or derivatizingagents; 4) functionalizing or derivatizing the polymer; 5) optionally,adding one or more of the group consisting of reactive plasticizers andprepolymers dissimilar to the prepolymer synthesized in step 2); and 6)removing the solvent, residual impurities, unreacted functionalizing orderivatizing agents and byproducts, to give the precursor mixturecontaining a crosslinkable prepolymer. Optionally, a dead polymer, whichis substantially unreactive, is also added to the precursor mixture at adesired point before removing the solvent.

The resulting crosslinkable prepolymer preparation is then introducedinto a mold having a desired geometry; the mold is compressed so thatthe crosslinkable prepolymer preparation takes on the shape of theinternal cavity of the mold; and the crosslinkable prepolymerpreparation is exposed to a source of polymerizing energy; to give acured molding.

Processes in accordance with this invention include both continuousprocesses and step-wise processes. Continuous processes include those inwhich a first stage is the polymerization of a monomer or combination ofmonomers in the presence of the non-aqueous diluent and optionally anadditional solvent, while in succeeding stages the resulting polymer isfunctionalized to render the polymer capable of crosslinking. Thesolvent and impurities (such as unreacted monomer and functionalizingagent, residual initiator, polymerization catalyst, and any reactionby-products) in these continuous processes are removed by vacuumdistillation, leaving only the crosslinkable polymer and the non-aqueousdiluent in the appropriate proportions for casting and isometricexchange.

Step-wise processes permit the use of different solvents for eachreaction as well as isolation and purification procedures between eachreaction. Thus, unwanted components such as residual monomers,oligomers, and polymerization solvent can be removed after thepolymerization step, and unreacted functionalizing agent, products ofunwanted reactions, and solvent can be removed after thefunctionalization step. Also, the use of different solvents allows oneto select solvents that are best suited for each stage.

The present invention provides an efficient means for producing novelpolymeric precursor mixtures. The components and compositions ofreaction media are selected to achieve the desired processing conditionsto produce precursor mixtures. The components of precursor mixtures arechosen and the composition adjusted accordingly to achieve the desiredprocessability of precursor mixtures, desired degree of reactivity(including effects on cure time and shrinkage), as well as the finalphysical, chemical, and optical properties of the moldings so produced.

An advantage of the process of this invention is the low shrinkage whichcan be realized upon cure. As will be discussed in more detail below,the overall concentration of reactive species is quite low in thepolymeric precursor mixture. Another advantage is the speed with whichthe polymeric precursor mixture can be cured. Thus, the desired degreeof reaction can be achieved very quickly using appropriate reactioninitiators and a source of polymerizing energy.

In one embodiment of this invention, a process is designed to producepolymeric precursor mixtures for biomedical applications such as contactlenses which do not require purification steps upon curing and exhibitlittle net change in the volume after equilibration in physiologicalsalt solutions.

In another embodiment of this invention, the precursor mixture isformulated as a semi-solid polymerizable composition. The use of asemi-solid precursor mixture has advantages over liquid precursormixtures in that conventional liquid handling problems during moldfilling, such as evaporative rings, inclusion of bubbles or voids, andSchlieren effects, can be avoided and the semi-solid precursor mixturedoes not require a gasket in the mold assembly to produce articles, suchas ophthalmic lenses. Other advantages of the semi-solid precursormixture of this invention will be discussed below.

In yet another embodiment of the present invention, the precursormixture comprises a prepolymer, a dead polymer, and optionally, areactive plasticizer and/or a non-reactive diluent. The component andcomposition of the precursor mixture are chosen accordingly to create adesired phase morphology which is locked-in by the rapid curingaccomplished by the process of this invention.

With respect to the structure of crosslinked polymer network in thecured molding, the polymeric precursor mixtures of this inventionprovide crosslinked polymer networks which are distinct from thoseobtained by the conventional monomer-based casting processes in whichmoldings are produced by direct polymerization of monomer mixturescomprising multifunctional monomers (i.e., crosslinkers) andmonofunctional monomers. Because multifunctional monomers are morereactive than monofunctional monomers, clustering of multifunctionalmonomers often occurs during direct polymerization of monomer mixturesto produce moldings. In the present invention, crosslinking bonds areformed at the functionalized sites on the prepolymer backbone. Becausepolymers can be functionalized uniformly, the crosslinking bonds in thepolymer networks of this invention are more uniformly distributed thanthose of the conventional monomer-based casting systems. Thus, in yetanother aspect, the invention also relates to the moldings produced fromthe polymeric precursor mixtures of this invention.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

The terms “a” and “an” as used herein and in the appended claims mean“one or more”.

The term “monomer” is used herein to include mixtures of two or moredifferent monomers that polymerize to form a copolymer as well as singlespecies that form a polymer consisting solely of a single repeatingunit. The term “polymer” is used herein to include copolymers as well aspolymers consisting solely of a single repeating unit.

In the present invention, polymerizable groups are incorporated into theprecursor mixture through the prepolymer obtained by the continuousprocess of this invention, which comprises a polymerization step and afunctionalization or derivatization step. The polymerization step firstproduces a polymer from a monomer mixture. The polymer so produced isthen functionalized or derivatized with reactive groups to give theprepolymer, which is a functionalized crosslinkable polymer. Optionally,the precursor mixture also comprises reactive plasticizers andadditional prepolymers which are dissimilar to the prepolymersynthesized in the present process.

The terms “functionalization” and “derivatization” are used hereininterchangeably, and the term “functionalized with reactive groups” asused herein refers to the modification of a polymer to provide aplurality of reactive groups, particularly crosslinkable groups, on thebackbone of the polymer. The term “crosslinkable” refers to polymersthat are either devoid of crosslinking but capable of crosslinking undercrosslinking conditions, or contain a limited degree of crosslinking andare capable of further crosslinking under appropriate conditions.

In addition, the polymeric precursor mixture may comprise non-reactiveor substantially non-reactive diluents. The diluents may serve asbulking agents that do not contribute to the reactivity of the system,or they may function as compatibilizers in order to reduce phaseseparation tendencies of the other components in the mixture. While thediluents may play some role in the polymerization process, they willtypically be assumed to be non-reactive, that is, they will notcontribute significantly to the polymer chains or networks formed uponpolymerization.

Oligomers or polymers possessing reactive groups, or being otherwisereactive, are at certain locations herein referred to as “prepolymers.”For the purposes of this disclosure, prepolymers shall furthermore referto molecules having a formula weight greater than 300 or molecules whichcomprise more than one repeat unit linked together. Functionalizedmolecules having a formula weight below 300 and comprising only onerepeat unit shall be referred to as “reactive plasticizers,” asdiscussed below. The prepolymers may possess terminal and/or pendantreactive functionalities, or they may simply be prone to grafting orother reactions in the presence of the polymerizing system used toconstitute the polymeric precursor mixture. The polymeric precursormixture of this invention contains at least one prepolymer which isobtained by functionalizing the polymer synthesized from a monomermixture according to the process of this invention. The precursormixture may also contain other prepolymers which are dissimilar to theprepolymer synthesized in the present process.

Alternatively, small molecule reactive species (i.e., monomers having aformula weight below about 300) may be optionally added to the polymericprecursor mixture in order to impart an added degree of reactivityand/or to achieve the desired semi-solid consistency and compatibility,in which case the small molecule reactive species may serve toplasticize the polymeric components. The small molecule species mayotherwise serve as polymerization extenders, accelerators, orterminators during reaction. Regardless of their ultimate effect uponthe polymeric precursor mixture and the subsequent polymerizationreaction, such components shall hereinafter be referred to as “reactiveplasticizers.”

The polymeric precursor mixture may furthermore comprise non-reactive orsubstantially non-reactive polymers, which shall hereinafter be referredto as “dead polymers.” The dead polymers may serve to add bulk to thepolymeric precursor mixture without adding a substantial amount ofreactive groups, or the dead polymers may be chosen to impart variouschemical, physical, optical, and/or mechanical properties to themoldings of interest. The dead polymers may also serve as diluents forthe polymerization step by decreasing the monomer concentration in thereaction medium. For semi-solid precursor mixtures, the dead polymersmay further be used to impart a desired degree of semi-solid consistencyto the precursor mixture.

Non-reactive, i.e., inert, diluents may be advantageously added to thepolymeric precursor mixtures of the present invention in order toachieve compatibility of the mixture components, achieve the desiredconcentration of reactive functionalities, and to achieve the desiredsemi-solid consistency. Diluents are chosen based upon theircompatibility with and plasticizing effects on the prepolymer, deadpolymer, and reactive plasticizer constituents in the semi-solidprecursor mixture. Typically, compatible mixtures are desired for theproduction of the moldings of interest, except where phase separation iseither unavoidable or desired to achieve some desired material propertyin the final molding. For the production of ophthalmic lenses, clearsystems upon cure are desirable, which can be easily achieved byselecting non-reactive diluents that are compatible with the prepolymersand dead polymers of the polymeric precursor mixture.

While the inert diluents are ostensibly unreactive in the polymerizingsystem of the polymeric precursor material, some minor degree ofreaction may in fact occur, and such reaction will generally beacceptable and unavoidable. Diluents may also affect the polymerizationreaction by acting as chain terminating agents (a known phenomenon whenwater is present in anionic polymerization systems, for example), thusslowing the rate of cure, the final degree of cure, or the molecularweight distribution ultimately obtained. Fortunately, because thepolymeric systems of the present invention require little overallreaction from start to finish compared to predominantly monomericsystems, interference effects of the diluents will be greatly reduced,often to the point of having no measurable impact on the curingreaction. This greatly facilitates the choice of diluents that may beemployed in the process of this invention, since reaction inhibitioneffects are less likely to arise.

By way of example, non-reactive diluents may include, but are notlimited to: alcohols such as methanol, ethanol, propanol, butanol,pentanol, etc. and their methoxy and ethoxy ethers; glycols such asmono-, di-, tri-, tetra-, . . . polyethylene glycol and its mono- anddi-methoxy and -ethoxy ethers, mono-, di-, tri-, tetra-, . . .polypropylene glycol and its mono- and di-methoxy and -ethoxy ethers,mono-, di-, tri-, tetra-, . . . polybutylene glycol and its mono- anddi-methoxy and -ethoxy ethers, etc., mono-, di-, tri-, tetra-, . . .polyglycerol and its mono- and di-methoxy and -ethoxy ethers;alkoxylated glucosides such as the ethoxylated and propoxylatedglucosides described in U.S. Pat. No. 5,684,058, and/or as sold underthe “Glucam” trade name by Amerchol Corp.; ketones such as acetone,methyl ethyl ketone, methyl propyl ketone, methyl isobutyl ketone;esters such as ethyl acetate or isopropyl acetate; dimethyl sulfoxide,N-methylpyrrolidone, N,N-dimethyl formamide, N,N-dimethyl acetamide,cyclohexane, diacetone dialcohol, boric acid esters (such as withglycerol, sorbitol, or other polyhydroxy compounds, as disclosed in U.S.Pat. Nos. 4,495,313, 4,680,336, and 5,039,459), and the like.

The diluents employed for the production of contact lenses shouldultimately be water-displaceable, although the diluents used in theproduction of moldings of interest may be first extracted with a solventother than water, followed by water extraction in a second step, ifdesired.

“Over-the-counter” use of demulcents within ophthalmic compositions isregulated by the US Food & Drug Administration (FDA). For example, theFederal Register (21 CFR Part 349) entitled Ophthalmic Drug Products forOver-the-Counter Use: Final Monograph lists the accepted demulcentsalong with appropriate concentration ranges for each. Specifically,§349.12 lists the following approved “monograph” demulcents: (a)cellulose derivatives: (1) carboxymethyl cellulose sodium, (2)hydroxyethyl cellulose, (3) hydroxy propyl methyl cellulose,methylcellulose; (b) dextran 70; (c) gelatin; (d) polyols, liquid: (1)glycerin, (2) polyethylene glycol 300, (3) polyethylene glycol 400, (4)polysorbate 80, (5) propylene glycol; (e) polyvinyl alcohol; and (f)povidone (polyvinyl pyrrolidone). §349.30 further provides that in orderto fall within the monograph, no more than three of the above-identifieddemulcents may be combined.

Diluents used in accordance with the present invention are preferablyFDA-approved ophthalmic demulcents or mixtures of ophthalmic demulcentswith water or saline solutions. In cases where water interferes with thepolymerization process (which is less likely using polymeric precursormixtures of the invention than in conventional polymerization schemesusing liquid monomer precursors), pure demulcents or mixtures ofdemulcents with prepolymers, dead polymers, and/or reactive plasticizersmay be employed. The concentration of the demulcents within the moldingduring cure may be much higher than the concentrations allowed by theFDA in cases where the moldings will be diluted or equilibrated in wateror saline solution prior to use by the consumer, such as the case wherecontact lens moldings are placed into a package with an excess of salinesolution for storage and shipping.

If semi-solid precursor mixtures are desired, the components andcomposition are also adjusted accordingly to achieve the desiredsemi-solid consistency. By “semi-solid” is meant that the mixture issubstantially uncrosslinked, deformable, and fusible, yet can be handledas a discrete, free-standing entity during short operations such asinsertion into a mold. For pure polymeric systems, the modulus ofelasticity of a pure polymeric material is roughly constant with respectto molecular weight, above a certain value, known as the molecularweight cutoff. Thus, for the purpose of this disclosure, and in oneaspect of the present invention, semi-solids will be defined asmaterials that, at fixed conditions such as temperature and pressure,exhibit a modulus below the constant modulus value seen for a given purepolymeric system at high molecular weights, i.e., above the molecularweight cutoff. The decrease in modulus used to achieve a semi-solidconsistency may be achieved by incorporation of plasticizers (reactiveor non-reactive diluents) into the semi-solid precursor mixture thatserve to plasticize one or more of the prepolymer or dead polymercomponents. Alternatively, low molecular weight analogs below themolecular weight cutoff for a given prepolymer may be used in place ofthe fully polymerized version to achieve a reduction in modulus at theprocessing temperature. With these considerations in mind, preferredmolecular weights are within the range of about 10,000 to about1,000,000, more preferably from about 10,000 to about 300,000, and mostpreferably from about 50,000 to about 150,000. System parameters thatcan be varied to control the molecular weight are the amount ofinitiator used relative to the amount of monomer, the presence or lackof a chain transfer agent, the reaction temperature, the time duringwhich the reaction is allowed to proceed, and the type and concentrationof solvent used. The influence of each of these factors and theappropriate choice of each one to achieve a polymer of a particularmolecular weight range will be readily apparent to those skilled in theart.

Using semi-solid precursor mixtures, the process of the presentinvention is advantageous with respect to the conventional moldingtechniques because the semi-solid precursor materials provide a smallbut finite resistance to flow such that the semi-solid material does notflow out of the mold upon its introduction, unlike liquid precursorsused with static casting techniques. Yet, the semi-solid materials arecompliant enough to be easily compressed and deformed to take on thedesired mold cavity shape or surface features without undue resistancewhen two static compression molds are brought together. Furthermore,unlike typical thermoplastics, the semi-solid materials do not requirean excessive or undesirable amount of heating and/or compressive force,typically seen with compression or injection molding techniques usingconventional materials. Thus, the semi-solid materials of the presentinvention can be viewed as combining the easy deformability of liquidswith the easy handling aspects of solids into a system that is reactive(but shows low shrinkage) and can be cured into a crosslinked entityupon cure.

With respect to a liquid precursor mixture, the advantage of thesemi-solid precursor mixture is that conventional liquid handlingproblems during mold filling, such as evaporative rings, inclusion ofbubbles or voids, and Schlieren effects, can be avoided with the use ofthe semi-solid precursor mixture. In addition, for the molding ofophthalmic lenses, the semi-solid precursor mixture does not require agasket in the mold assembly.

The molding process, which makes use of semi-solid precursor mixtures,also has an advantage over the previous process which uses partiallycured gel preforms disclosed by U.S. Pat. No. 4,260,564 for theproduction of ophthalmic lenses. In the partially cured gel-basedmolding process, a liquid monomer mixture in a mold assembly is firstpartially cured to form a gel, which takes a geometry close to the shapeof the final object of interest. This partially cured gelled preform isthen transferred to another mold assembly where the preform is moldedfurther to a desired shape and fully cured. Because gels are notfusible, defects such as scratches on the surface of partially cured gelpreforms and internal stress introduced during the molding operationremain in the cured articles produced from partially cured gel preforms.The semi-solid precursor mixtures of this invention overcome theseproblems because semi-solids are substantially uncrosslinked, malleable,and fusible.

Another advantage of the semi-solid precursor mixture is that when freeradical-based polymerization schemes are used to cure the semi-solidprecursor mixture, inhibition effects due to oxygen are reduced. Whilenot wishing to be bound by theory, it is believed that this effectresults from a low oxygen mobility within the semi-solid material priorto and during cure, as compared to conventional liquid-based castingsystems. Thus, complex and costly schemes (both molding of the molds aswell as molding of the final part, as described in U.S. Pat. Nos.5,922,249 and 5,753,150, for instance) currently used to exclude oxygenfrom molding processes can be eliminated, and reaction will stillproceed to completion in a timely fashion as mentioned above.

In the present invention, which preferably makes use of semi-solidprecursor mixtures, reaction proceeds quickly because the reaction is acrosslinking reaction and the precursor polymer contains only a smallnumber of crosslinking sites, and inhibition effects due to oxygen arereduced in the semi-solid precursor mixture. By “quick curing time” ismeant that the polymeric precursor mixtures of the present inventioncure faster than a liquid composition in cases where the liquidformulation possesses the same type of reactive functional groups andthe other curing parameters, such as energy intensity and part geometry,are constant. Typically, about 10 minutes or less of exposure to asource of polymerizing energy is needed in order to achieve the desireddegree of cure when photoinitiated systems comprising the semi-solidprecursors are used. More preferably, the curing occurs in less thanabout 100 seconds of exposure, and even more preferably in less thanabout 10 seconds. Most preferably, the curing occurs in less than about2 seconds of exposure to a source of polymerizing energy. Such rapidcuring times can be more easily realized for thin moldings such ascontact lenses.

Because the semi-solid material can be cured rapidly and contains arelatively small amount of monomers, a great processing advantage can berealized in the recycling or reuse of lens molds after each moldingcycle. When released from a mold upon cure, the semi-solid precursormixture leaves much less residual monomers on the mold surface than theliquid precursor mixture. Thus, one embodiment of the present inventionis a process in which contact and ophthalmic lens molds are reused formore than one molding cycle, with optional cleaning steps in betweenuses, in accordance with the use of semi-solid precursor mixtures asdiscussed herein.

The polymeric precursor mixtures disclosed by the present invention maybe advantageously utilized to produce polymerized and/or crosslinkedmoldings. Therefore, in yet another aspect, the present inventionrelates to moldings produced from curing a polymeric precursor mixture.For the purpose of producing contact lenses or intraocular lenses, thecompositions of the fully cured moldings are chosen such that theybecome hydrogels when placed into essentially aqueous solutions; thatis, the moldings will absorb about 10 to 90 weight percent water uponestablishing equilibrium in a pure aqueous environment, but will notdissolve in the aqueous solution. Said moldings shall be hereinafterreferred to as “hydrogels.”

The polymeric precursor mixtures of this invention may also beadvantageously utilized to produce homogeneous hydrogels in which thecrosslinking bonds are uniformly or substantially uniformly distributed.As stated previously, in the prior art gels synthesized by directpolymerization of monomer mixtures, crosslinking bonds may not beuniformly distributed because of the clustering of multifunctionalmonomers.

For the purposes of this disclosure, essentially aqueous solutions shallinclude solutions containing water as the majority component, and inparticular aqueous salt solutions. It is understood that certainphysiological salt solutions, i.e., saline solutions, may be preferablyused to equilibrate or store the moldings in place of pure water. Inparticular, preferred aqueous salt solutions have an osmolarity of fromabout 200 to 450 milli-osmolarity in one liter; more preferred solutionsare from about 250 to 350 milliosmol/L. The aqueous salt solutions areadvantageously solutions of physiologically acceptable salts such asphosphate salts, which are well-known in the field of contact lens care.Such solutions may further comprise isotonicizing agents such as sodiumchloride, which are again well known in the field of contact lens care.Such solutions shall hereinafter be referred to generally as salinesolutions, with no preference given to salt concentrations andcompositions outside of the currently known art in the field of contactlens care.

The moldings of the present invention may be advantageously formed intocontact lenses or intraocular lenses that exhibit “minimal expansion orcontraction”; that is, they exhibit little or no expansion orcontraction of the hydrogel upon placement into saline solution. Thismay be accomplished by adjusting the amount of diluent present such thatno net volume change of the hydrogel occurs when the molding isequilibrated in a saline environment. This goal can be readily achievedby using saline as the sole diluent so long as it is incorporated at thesame concentration in the semi-solid precursor mixture as itsequilibrium content after hydrogel formation, which can be readilydetermined by simple trial and error experimentation. Should one preferthe use of other diluents either with or without the presence of salinein the semi-solid precursor mixture, then the diluent concentrationleading to no net volume change of the hydrogel when equilibrated withsaline may not be the same as the equilibrium saline concentration but,again, can again be readily ascertained by simple trial and errorexperimentation.

“Extraction” is the process by which unwanted or undesirable species(usually small molecule impurities, polymerization by-products,unpolymerized or partially polymerized monomer, etc., sometimes referredto as extractables) are removed from a cured hydrogel prior to itsintended use. By “prior to its intended use” is meant, for example inthe case of a contact lens, prior to insertion into the eye. Extractionsteps are a required feature of prior art processes used to make contactlenses, for example (see U.S. Pat. Nos. 3,408,429 and 4,347,198), whichadd complications, processing time, and expense to the moldingproduction process.

An advantage of the present invention is that moldings can be producedthat do not require an extraction step, or require only a minimalextraction step, once the polymerization step is complete. By “minimalextraction step” and “minimum extraction” are meant that the amount ofextractables is sufficiently low and/or the extractable composition issufficiently non-toxic that any required extraction may be accommodatedby the fluid within the container in which the lens is packaged forshipment to the consumer. The phrases “minimal extraction step” and“minimum extraction” may furthermore comprise any washing or rinsingthat occurs as a part of any aspect of the demolding operation, as wellas any handling steps. For example, liquid jets are sometimes used tofacilitate movement of the lens from one container to another, demoldingfrom one or more of the lens molds, etc., said jets generally comprisingfocused water or saline solution streams. During these processes, someextraction or rinsing away of any extractable lens materials may bereasonably expected to occur, but in any case shall be deemed to fallunder the class of materials and processes requiring a minimalextraction step, as presented in this disclosure.

As an example, in one embodiment of the present invention, the polymericprecursor mixture comprises 30-70 weight % of a prepolymer, aphotoinitiator, and a non-reactive diluent that is selected from thegroup consisting of water and FDA-approved ophthalmic demulcents. Uponcuring, the molding may be placed directly into a contact lens packagingcontainer containing about 3.5 mL of saline fluid for storage, with theaid of one or more liquid jets to aid in the demolding process and tofurther facilitate lens handling without mechanical contact (see forexample, U.S. Pat. No. 5,836,323), whereupon the molding willequilibrate with the surrounding fluid in the package. Since the moldingvolume of a contact lens (e.g., about 0.050 mL) is small relative to thefluid volume in the lens package, the demulcent concentration will be atleast about 1 wt % or lower in both the solution and the lens afterequilibration, which concentration is acceptable for direct applicationto the eye by the consumer. Thus, while from a strict viewpoint anextraction step is used in this embodiment, the extraction step isreduced to a minimal extraction step—that which occurs inherently duringthe demolding, handling and packaging processes. The fact that noseparate extraction step is used per se represents a significantadvantage of the present invention disclosed herein.

In one embodiment, the present invention relates to prepolymers that arenot substantially water-soluble. By “water-soluble” is meant that theprepolymers are capable of being dissolved in water or saline solutionsover the entire concentration range of about 1-10 wt % prepolymer underambient conditions, or more preferably about 1-70% prepolymer in wateror saline solutions. Thus, for purposes of this disclosure,“water-insoluble” or “non water-soluble” prepolymers shall be thosewhich do not completely dissolve in water over the concentration rangeof about 1-10% in water at ambient conditions. In a preferredembodiment, hydrogels made from prepolymers that are water-insoluble maybe water-swellable such that they are capable of producing a homogeneousmixture upon absorbing from 10 to 90% water. Generally, suchwater-swellable hydrogels will exhibit a maximum water absorption (i.e.,equilibrium water content) that is a function of the chemicalcomposition of the polymers making up the hydrogel, as well as thehydrogel crosslink density. Preferred hydrogels in accordance with thisinvention are those exhibiting an equilibrium water content of fromabout 20 to 80 wt % water in a water or saline solution. Whencrosslinked, such water-insoluble but water-swellable materialsdesirably produce clear hydrogels, which are useful products of thepresent invention.

In a preferred embodiment of the invention, a homogenous mixture of oneor more prepolymers and one or more non-reactive diluents is constitutedthat is substantially free from monomeric, oligomeric, or polymericcompounds used in (and by-products formed during) the preparation of theprepolymer, as well as being free of any other unwanted constituentssuch as impurities or diluents that are not ophthalmic demulcents. By“substantially free” is meant herein that the concentration of theundesirable constituents in the semi-solid precursor mixture ispreferably less than 0.001% by weight, and more preferably less than0.0001% (1 ppm). The acceptable concentration range for such undesirableconstituents will ultimately be determined by the intended use of thefinal product. This mixture preferably contains only diluents that arewater or are recognized by the FDA as acceptable ophthalmic demulcentsin limited concentrations in the eye. The mixture is furthermoreconstituted so as to not contain any additional co-monomers or reactiveplasticizers. In this manner a polymeric precursor mixture isconstituted which contains no or essentially no unwanted constituents,and thus the molding produced therefrom contains no or essentially nounwanted constituents. Moldings are therefore produced which do notrequire the use of a separate extraction step, aside from theextraction/equilibration process which occurs within the packagingcontainer and during demolding and intermediate handling steps after thecured molding has been produced.

In another preferred embodiment of the present invention, the diluentcomposition and concentration in the polymeric precursor mixture ischosen such that upon curing and subsequent equilibration in salinesolution, little net change in hydrogel volume occurs. Preferably,hydrogel volume changes by no more than 10% upon equilibration in aphysiologically acceptable saline solution. More preferably, thehydrogel volume changes by less than 5%, and even more preferably byless than 2%. Most preferably, the hydrogel volume changes by less than1% upon equilibration in saline after molding, cure and demolding.

Minimal hydrogel volume changes upon equilibration in saline are madepossible by the novel polymeric precursor mixtures of the presentinvention because the polymeric polymerizable compositions (1) exhibitlow shrinkage upon cure, and (2) can be formulated to contain the amountof diluent necessary to compensate for the equilibrium content of water.

In yet another preferred embodiment, the diluent concentration isadjusted such that a fixed amount of hydrogel swelling occurs uponequilibration in water. This is sometimes helpful to aid in thedemolding process, and yet the hydrogel volume change can beaccommodated by an appropriate mold design which takes into account asmall but fixed amount of swelling of the finished molding.

In a presently preferred embodiment, the polymeric precursor mixturecomprises a water-insoluble but water-swellable prepolymer that is afunctionalized copolymer of polyhydroxyethyl methacrylate (pH EMA). Thecopolymer can comprise methacrylic acid, acrylic acid, n-vinylpyrrolidone, dimethyl acrylamide, vinyl alcohol, and other monomersalong with HEMA. A presently preferred embodiment comprises pHEMAcopolymerized with approximately 2% methacrylic acid (MAA). In addition,polymerizable additives such as reactive dyes and reactive UV absorberscan also be copolymerized with the monomers. This copolymer issubsequently functionalized with methacrylate groups or acrylate groupsto create a reactive prepolymer suitable for the production ofophthalmic moldings useful as contact lenses. The reactive groups arecovalently attached to the polymer backbone through the hydroxyl groupsof HEMA. The pHEMA-co-MAA copolymer is diluted with the polyethyleneglycol which has an average molecular weight of 400 (PEG 400) at aconcentration of about 50 wt % and a photoinitiator such as IRGACURE®184, DAROCUR® 1173, and/or IRGACURE® 1750 is added at a concentration ofapproximately 1 weight %.

In one preferred embodiment of this invention, the polymeric precursormixture containing pHEMA-co-MAA copolymer is obtained by the methodwhich comprises the steps of:

-   -   mixing together i) one or more different types of monomers and a        thermal initiator, ii) at least one non-reactive low-volatility        diluent in an amount such that after molding it can provide an        isometric exchange with saline solution, and iii) a volatile        non-aqueous solvent in an amount to prevent an insoluble gel        from forming during the ensuing polymerization and        functionalization steps;    -   polymerizing the monomers to give a polymer;    -   adding one or more different types of functionalizing or        derivatizing agents;    -   functionalizing or derivatizing the polymer and adding a        photoinitiator; and    -   evaporating off the solvent, residual impurities, unreacted        functionalizing or derivatizing agents and byproducts, to give        the polymeric precursor mixture containing the non-reactive        diluent.

The advantage of the process of this invention is that after thepolymerization step, it is not necessary to recover and purify polymersand blend polymers with non-reactive diluents because the polymers aresynthesized and functionalized continuously in the presence of thenon-reactive diluents which constitute the final precursor mixtures. Theuse of volatile solvent is advantageous for producing the polymericprecursor mixture in which a polymer is synthesized from a monomer, suchas HEMA, which contains a multifunctional monomer as impurity. Thepresence of the volatile solvent prevents the formation of an insolublegel even when a small amount of multi-functional monomers exist in thereaction medium. And, its volatile character allows it to be easilyremoved without excessive additional processing.

The material obtained in this manner is a homogeneous precursor mixturewhich is optically clear. Small portions of the precursor mixture can beremoved from the bulk mass and inserted into a mold cavity as a discretequantity. Upon closing the mold, the precursor deforms and takes theshape of the internal cavity defined by the mold halves. When the sampleis irradiated with a source of polymerizing energy such as heat or UVlight, the precursor mixture cures into a water-swellable crosslinkedgel that can subsequently be demolded and placed into saline solutionfor equilibration. The resulting hydrogel can be designed to absorbapproximately 30-70% water at equilibrium, while exhibiting mechanicalproperties such as elongation-to-break and modulus similar tocommercially available contact lens materials. Thus, the molding soproduced is useful as an ophthalmic lens, especially a contact orintraocular lens, said lens being produced with a polymeric precursormaterial that exhibits low shrinkage during a rapid curing step, andsaid lens requiring no separate extraction step aside from theequilibration step in the package.

Another preferred embodiment uses silicone-based monomers andhydrophilic silicones, which are copolymers of a hydrophilic componentand a silicone component exhibiting high oxygen permeability, as thestarting monomers, dead polymers, or when possessing additionalfunctional groups, as prepolymers or reactive plasticizers. Thesematerials are particularly useful for contact lenses. Suitablesilicone-based monomers and prepolymers for producing the polymericprecursor mixtures of the present invention are disclosed in U.S. Pat.Nos. 4,136,250, 4,153,641, 4,740,533, 5,010,141, 5,034,461, 5,057,578,5,070,215, 5,314,960, 5,336,797, 5,356,797, 5,371,147, 5,387,632,5,451,617, 5,486,579, 5,789,461, 5,807,944, 5,962,548, 5,998,498,6,020,445, and 6,031,059, as well as PCT Appl. Nos. WO094/15980,WO097/22019, WO099/60048, WO099/60029, and WO001/02881, and EuropeanPat. Appl. Nos. EP00940447, EP00940693, EP00989418, and EP00990668.

Another preferred embodiment uses perfluoroalkyl polyethers, which arefluorinated to give good oxygen permeability and inertness, yet exhibitan acceptable degree of hydrophilicity due to the polymer backbonestructure and/or hydrophilic pendant groups. Such materials may bereadily incorporated into the polymeric precursor mixtures of thepresent invention as the dead polymers, or when possessing additionalfunctional groups, as prepolymers or reactive plasticizers. For examplesof such materials, see U.S. Pat. Nos. 5,965,631, 5,973,089, 6,060,530,6,160,030, and 6,225,367.

In principle, mixtures of any monomers may be used in the polymerizationstep of this invention, provided that the synthesized polymers containfunctionalizable groups. By “functionalizable groups” is meant thegroups which are capable of undergoing functionalization orderivatization reactions to introduce functional groups on the polymerbackbone. The monomer may be acrylate, methacrylate, acrylic anhydride,acrylamide, vinyl, vinyl ether, vinyl ester, vinyl halide, vinyl silane,vinyl siloxane, (meth)acrylated silicones, vinyl heterocycles, diene,allyl and the like. Other less known but polymerizable systems can beemployed, such as epoxies (with hardeners) and urethanes (reactionbetween isocyanates and alcohols).

Polymerization mechanisms that may be employed by the present inventionpurely by way of example include free-radical polymerization, cationicor anionic polymerization, cycloaddition, Diels-Alder reactions,ring-opening-metathesis polymerization, and vulcanization. Polymers maybe homopolymers or copolymers of linear, branched, dendritic, or lightlycrosslinked structures.

To demonstrate the great diversity of monomers that can be used in thepresent invention, we will name only a few from a list of hundreds tothousands of commercially available compounds. For example,mono-functional monomers include (meth)acrylates such as methyl(meth)acrylate and 2-hydroxyethyl methacrylate (HEMA), vinyl lactamssuch as N-vinyl-2-pyrrolidone, (meth)acrylamide and its analogues suchas N-isopropyl acrylamide, vinyl acrylic acids such as (meth)acrylicacid, vinyl acetate, vinyl benzoate, styrene, α-methyl styrene, maleicanhydride, and acrylonitrile. Note, notations such as “(meth)acrylate”or “(meth)acrylamide” are used to denote optional methyl substitutions.

Other mono-functional (meth)acrylic monomers include: ethyl(meth)acrylate; propyl (meth)acrylate; butyl (meth)acrylate; octyl(meth)acrylate; isodecyl (meth)acrylate; hexadecyl (meth)acrylate;stearyl (meth)acrylate; propyl (meth)acrylate; pentyl (meth)acrylate;tetrahydrofurfuryl (meth)acrylate; caprolactone (meth)acrylate; benzyl(meth)acrylate; phenyl (meth)acrylate; 2-phenylphenyl (meth)acrylate;phenoxyethyl (meth)acrylate; 1-naphthyloxyethyl (meth)acrylate;cyclohexyl (meth)acrylate; isobornyl (meth)acrylate; norbornyl(meth)acrylate; adamantyl (meth)acrylate;tricyclo[5.2.1.0^(2,6)]-decan-8-yl (meth)acrylate; ethylene glycolphenyl ether (meth)acrylate; 3-hydroxy-2-naphtyl (meth)acrylate;2-hydroxyethyl acrylate (HEA); 2-hydroxybutyl (meth)acrylate;2-hydroxypropyl (meth)acrylate; 3-phenoxy-2-hydroxy-phenoxyethyl(meth)acrylate; 3-hydroxypropyl (meth)acrylate; 4-hydroxybutyl(meth)acrylate; 4-t-butyl-2-hydroxycyclohexyl (meth)acrylate;2-ethylhexyl (meth)acrylate; 2-ethoxyethyl (meth)acrylate; ethoxyethyl(meth)acrylate; methoxyethyl (meth)acrylate; methoxy triethyleneglycol(meth)acrylate; hydroxytrimeththylene (meth)acrylate; dimethylaminoethyl(meth)acrylate; glycidyl (meth)acrylate; 2-phosphatoethyl(meth)acrylate; mono-, di-, tri-, tetra-, penta-, . . .polyethylenglycol mono(meth)acrylate; 1,2-butylene (meth)acrylate; 1,3butylene (meth)acrylate; 1,4-butylene (meth)acrylate; mono-, di-, tri-,tetra-, . . . polypropylene glycol mono(meth)acrylate; glyceryl(meth)acrylate; gylcerine mono(meth)acrylate;2-ethyl-2-(hydroxy-methyl)-1,3-propanediol trimethyl(meth)acrylate.

Other types of monomers also include: methylacrylamide;N,N-dimethyl(meth)acrylamide; diacetone (meth)acrylamide;N-methyl(meth)acrylamide; N,N-dimethyl-diacetone(meth)acrylamide;N-(1,1-dimethyl-3-oxobutyl)(meth)acrylamide;N-(formylmethyl)(meth)acrylamide; 4- and 2-methyl-5-vinylpyridine;N-(3-(meth)acrylamidopropyl)-N,N-dimethylamine;N-(3-(meth)acrylamidopropyl)-N,N,N-trimethylamine;N-(3-(meth)acrylamido-3-methylbutyl)-N,N-dimethylamine; 1-vinyl-, and2-methyl-1-vinlymidazole; N-vinyl imidazole; N-vinyl succinimide;N-vinyl diglycolylimide; N-vinyl glutarimide; N-vinyl-3-morpholinone;N-vinyl-5-methyl-3-morpholinone; dimethyldiphenyl methylvinyl siloxane;α-(dimethylvinylsilyl)-ω-[(dimethylvinyl-silyl)oxy]-dimethyl diphenylmethylvinyl siloxane; vinyl propionate; vinyl alcohol;2-((meth)acryloyloxy)ethyl vinyl carbonate;vinyl[3-[3,3,3-trimethyl-1,1-bis(trimethylsiloxy)disiloxany]propyl]carbonate;4,4′-(tetrapentacontmethylheptacosasiloxanylene)di-1-butanol;N-carboxy-β-alanine N-vinyl ester; 2-methacryloylethylphosphorylcholine; methacryloxyethyl vinyl urea; vinyltoluene;1-vinylnaphthalene; metallic salts of (meth)acrylic acid; monomerscontaining quarternary ammonium salts; and the like.

The notation “mono-, di-, tri-, tetra-, . . . poly-” is used to denotemonomers, dimers, trimers, tetramers, etc., up to and including polymersof the given repeat unit.

When high-refractive index materials are desired, monomers may be chosenaccordingly to have high refractive indices. Examples of such monomers,in addition to those mentioned above, include brominated or chlorinatedphenyl (meth)acrylates (e.g., pentabromo methacrylate, tribromoacrylate, etc.), brominated or chlorinated naphthyl or biphenyl(meth)acrylates, tribromophenoxyethyl (meth)acrylate,tribromophenyldi(oxyethyl) (meth)acrylate, tribromoneopentyl(meth)acrylate, tribromobenzyl (meth)acrylate, bromoethyl(meth)acrylate, brominated or chlorinated styrenes, vinyl naphthylene,vinyl biphenyl, vinyl phenol, vinyl carbazole, vinyl bromide orchloride, vinylidene bromide or chloride, bromophenyl isocyanate,phenylthiol (meth)acrylate, 4-chlorophenylthiol (meth)acrylate,penta-chlorophenylthiol (meth)acrylate, naphthylthiol (meth)acrylate,and the like. Increasing the aromatic, sulfur and/or halogen content ofmonomers is a well-known technique for achieving high-refractive indexproperties.

The process of the present invention comprises the polymerization andfunctionalization or derivatization steps to produce prepolymers. Thecomponents of monomer mixtures are chosen such that the resultingpolymers contain functionalizable or derivatizable groups. In thefunctionalization or derivatization step, functionalizing agents arereacted with polymers to produce prepolymers by introducing reactivegroups on the polymer backbone. By “functionalizing agents” is meantmolecules which have groups reactive to the polymers and, upon reactingwith polymers, introduce reactive groups on the polymer backbone andthereby render the polymer capable of crosslinking. Thefunctionalization reaction may be carried out as a single step using asuitable functionalizing agent. Alternatively, the functionalizablegroup on the polymer backbone is transferred further to another type offunctionalizable group by reacting with a molecule, which is thenreacted with the functionalizing agent. The examples of functionalizablegroups include, but are not limited to: hydroxyls, amines, carboxylates,thiols (disulfides), anhydrides, urethanes, and epoxides.

For functionalizing the polymers containing hydroxyls, functionalizingagents comprise the hydroxyl-reactive groups such as, but not limitedto, epoxides and oxiranes, carbonyl diimidazole, oxidation withperiodate, enzymatic oxidation, acid halides, alkyl halides,isocyanates, halohydrins, and anhydrides. For functionalizing thepolymers containing amine groups, functionalizing agents comprise theamine-reactive groups such as isothiocyanates, isocyanates, acyl azides,N-hydroxysuccinimide esters, sulfonyl chlorides, ketones, aldehydes andglyoxals, epoxides and oxiranes, carbonates, arylating agents,imidoesters, carbodiimides, anhydrides, and halohydrins. Forfunctionalizing the polymers containing thiol groups, examples ofthio-reactive chemical reactions are haloacetyl and alkyl halidederivatives, maleimides, aziridines, acryloyl derivatives, arylatingagents, and thioldisulfide exchange regents (such as pyridyl disulfides,disulfide reductants, and 5-thio-2-nitrobenzoic acid).

In a presently preferred embodiment, the reactive groups on theprepolymer backbone are acrylate, methacrylate, acrylamide, and/or vinylether moieties which are found to give convenient, fast-curingUV-triggered systems.

To produce prepolymers for high-refractive index ophthalmic lenses, onepreferred embodiment uses the monomers that contain both halogen atomsand functionalizable groups such as hydroxyls. Examples include, but arenot limited to: 3-(2,4,6-tribromo-3-methylphenoxy)-2-hydroxypropyl(meth)acrylate; 3-(2,4-dibromo-3-methylphenoxy)-2-hydroxypropyl(meth)acrylate; 3-(3-methyl-5-bromophenoxy)-2-hydroxypropyl(meth)acrylate;2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxyethoxy-3,5-dibromophenyl)propane;2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxy-3,5-dibromophenyl)propane;and2-(4-hydroxydiethoxy-3,5-dibromophenyl)-2-(4-methacryloxydiethoxy-3,5-dibromophenyl)propane.

Monomer mixtures may also contain multifunctional monomers. In thatevent, the compositions and components of non-reactive diluents and/orsolvents are chosen accordingly to prevent insoluble gels from formingduring the polymerization and functionalization steps.

Optionally, polymerizable additives such as reactive (i.e.,polymerizable) dyes and reactive (i.e., polymerizable) UV absorbers maybe included in the monomer mixtures. In certain preferred embodiments ofthis invention, prepolymers are synthesized from monomer mixtures whichalso comprise reactive dyes and reactive UV absorbers for the productionof tinted UV absorbable contact lenses. One such monomer mixtureincludes 2-hydroxyethylmethacrylate, methacrylic acid, and the reactivedye known as “blue hydroxyethylmethacrylate” or “blue HEMA.” Anothersuch monomer mixture includes these three components plus the reactiveUV absorber known as “Norbloc.” The chemical name for blue HEMA is2-methyl-acrylic acid 2-{4-[5-(4-amino-9,10-dioxo-3-sulfo-4a,9,9a,10-tetrahydroanthracen-1-ylamino)-2-sulfophenylamino]-6-chloro-[1,3,5]triazin-2-yloxy}-ethylester, and the chemical formula is:

The chemical name for Norbloc is 2-methyl-acrylic acid2-(3-benzotriazol-2-yl-4-hydroxyphenyl)-ethyl ester, and the chemicalformula is:

One group of preferred prepolymers includes the polymers or copolymerscomprising sulfoxide, sulfide, and/or sulfone groups within or pendantto the polymer backbone structure that have been functionalized withadditional reactive groups. Gels resulting from sulfoxide-, sulfide-,and/or sulfone-containing monomers (without the added reactive groupsafter initial polymerization) have shown reduced protein adsorption inconventional contact lens formulations (see, U.S. Pat. No. 6,107,365 andPCT International Publication No. WO00/02937). These monomers arereadily incorporated into the polymeric precursor mixtures of thepresent invention as starting monomers for prepolymers and/or throughdead polymers.

Another group of preferred prepolymers consists the prepolymerscontaining one or more pendant or terminal hydroxy groups, some portionof which have been functionalized with reactive groups capable ofundergoing free-radical based polymerization. Examples of suchprepolymers include functionalized versions of polyhydroxyethyl(meth)acrylate, polyhydroxypropyl (meth)acrylate, polyethylene glycol,cellulose, dextran, glucose, sucrose, polyvinyl alcohol,polyethylene-co-vinyl alcohol, mono-, di-, tri-, tetra-, . . .polybisphenol A, and adducts of ε-caprolactone with C₂₋₆ alkane diolsand triols. Copolymers, ethoxylated, and propoxylated versions of theabove-mentioned polymers are also preferred prepolymers (see, forexample PCT International Publication No. WO098/37441).

Particularly preferred prepolymers are methacrylate- oracrylate-functionalized poly(hydroxyethyl methacrylate-co-methacrylicacid) copolymers. Most preferred prepolymers are copolymers ofhydroxyethyl methacrylate (HEMA) with about 0-2% methacrylic acid (MAA),where about 0.2-5% of the pendant hydroxyl groups of the copolymer havebeen functionalized with methacrylate groups to give a reactiveprepolymer suitable for the polymeric precursor mixtures and the processof this invention. A more preferable degree of methacrylatefunctionalization is about 0.5-2% of the hydroxyl groups. Forfunctionalizing the hydroxyls of HEMA, examples of functionalizingagents include methacrylic anhydride and glycidyl methacrylate.

In another preferred embodiment, the prepolymers are methacrylate- oracrylate-functionalized pHEMA-co-MAA copolymers copolymerized withreactive dyes and reactive UV absorbers consisting of about 0-2% MAA,where about 0.2-5% of the pendant hydroxyl groups of the copolymer havebeen functionalized with methacrylate or acrylate groups to give areactive prepolymer suitable for the polymeric precursor mixtures andthe process of this invention. More preferably, degree of methacrylatefunctionalization is about 0.5-2% of the hydroxyl groups and thefunctional group is methacrylate.

When high-refractive index prepolymers are an important consideration,as stated previously, increasing the aromatic content, the halogencontent (especially bromine), and/or the sulfur content are generallyeffective means well known in the art for increasing the refractiveindex of a polymeric material.

In the present invention, the polymeric precursor mixtures may alsocontain reactive plasticizers. Reactive plasticizers are added to thereaction medium upon completing the functionalization or derivatizationreaction. During the molding and curing operation, the presence ofreactive plasticizers may improve the processability by lowering thesoftening temperatures of precursor mixtures. With respect to thelowering of softening temperature, reactive plasticizers areparticularly useful for the precursor mixtures for ophthalmic lensesthat do not comprise non-reactive diluents but containtemperature-sensitive high-refractive index polymers. Thus, in oneembodiment of this invention, the polymeric precursor mixture comprisesa high-refractive index prepolymer and a reactive plasticizer. Morepreferably, the precursor mixtures are semi-solids.

The reactive plasticizers may also be used to accelerate thecrosslinking reaction of prepolymers and/or to increase the crosslinkingdensity of cured moldings. The prepolymers which by themselves do notform crosslinked gels may be crosslinked to form insoluble hydrogels inthe presence of a small amount of reactive plasticizers. For somebiomedical applications, the residual reactive groups in the curedmoldings may have to be minimized because of the decreasedbiocompatibility due to the presence of reactive groups. Thus, inanother embodiment of the present invention, the polymeric precursormixture comprises a prepolymer and a reactive plasticizer, andoptionally a non-reactive diluent, in which the precursor mixture doesnot cure to form an insoluble gel in the absence of the reactiveplasticizer.

When optically clear materials are desired in phase-separated systems,the mixture components (i.e., the prepolymers, dead polymers, the impactmodifiers, non-reactive diluents, and/or the reactive plasticizers) maybe chosen to produce the same refractive index between the phases(iso-refractive) such that light scattering is reduced. Wheniso-refractive components are not available, the diluents and reactiveplasticizers may nonetheless act as compatibilizers to help reduce thedomain size between two immiscible polymers to below the wavelength oflight, thus producing an optically clear polymer mixture that wouldotherwise have been opaque. The presence of reactive plasticizers mayalso in some cases improve the adhesion between the impact modifier andthe dead polymer, improving the resultant mixture properties.

The reactive plasticizers can be used singly or in mixtures. Thereactive functional group may be, but is not limited to, acrylate,methacrylate, acrylic anhydride, acrylamide, vinyl, vinyl ether, vinylester, vinyl halide, vinyl silane, vinyl siloxane, (meth)acrylatedsilicones, vinyl heterocycles, diene, allyl and the like. Other lessknown but polymerizable functional groups can be employed, such asepoxies (with hardeners) and urethanes (reaction between isocyanates andalcohols). In principle, any monomers may be used as reactiveplasticizers in accordance with the present invention, althoughpreference is given to those which exist as liquids at ambienttemperatures or slightly above, and which polymerize readily and rapidlywith the application of a source of polymerizing energy such as light orheat in the presence of a suitable initiator.

Reactive monomers, oligomers, and crosslinkers that contain acrylate ormethacrylate functional groups are well known and commercially availablefrom Sartomer, Radcure and Henkel. Similarly, vinyl ethers arecommercially available from Allied Signal/Morflex. Radcure also suppliesUV curable cycloaliphatic epoxy resins. Vinyl, diene, and allylcompounds are available from a large number of chemical suppliers.Examples of reactive plasticizers are discussed, for example, in PCTPublication No. WO 00/55653.

When high-refractive index materials are desired, the reactiveplasticizers may be chosen accordingly to have high refractive indices.As stated previously, increasing the aromatic, sulfur, and/or halogencontent of the reactive plasticizers is a well-known technique forachieving high-refractive index properties of polymeric materials.

In a presently preferred embodiment, reactive plasticizers containingacrylate, methacrylate, acrylamide, and/or vinyl ether moieties arefound to give convenient, fast-curing UV-triggered systems.

The reactive plasticizers can be mixtures themselves, composed ofmono-functional, bi-functional, tri-functional or other multi-functionalentities. For example, incorporating a mixture of monofunctional andmulti-functional reactive plasticizers will, upon polymerization, leadto a reactive plasticizer polymer network in which the reactiveplasticizer polymer chains are crosslinked to each other (i.e., asemi-IPN). During polymerization, the growing reactive plasticizerpolymer chains may react with the prepolymer to create an IPN. Thereactive plasticizer and prepolymer may also graft to or react with thedead polymer, creating a type of IPN, even if no unsaturated or otherapparently reactive entities are present within the dead polymer chains.Thus, the prepolymer and dead polymer chains may act as crosslinkingentities during cure, resulting in the formation of a crosslinkedreactive plasticizer polymer network even when only monofunctionalreactive plasticizers are present in the mixture with prepolymers and/ordead polymers.

In addition to prepolymers, systems of interest to the presentapplication may comprise one or more substantially unreactive polymericcomponents, i.e., dead polymers. The dead polymers may serve to add bulkto the polymeric precursor mixture without adding a substantial amountof reactive groups, or the dead polymers may be chosen to impart variouschemical, physical, optical, and/or mechanical properties to themoldings of interest.

The dead polymers may be linear, branched, or crosslinked. The simplestof such systems might be considered to be ordinary homopolymers. In suchcases, the dead polymer is generally chosen to be compatible with theprepolymer in the precursor mixture of interest, at least at somedesired processing conditions of temperature and pressure.“Compatibility” refers to the thermodynamic state where the mixturecontaining the dead polymer and prepolymer forms a homogeneous mixture.In practice it has been found that molecular segments with structuralsimilarity promote mutual dissolution. Hence, aromatic moieties on thedead polymer generally promote compatibility with aromatic prepolymers,and vice versa. Hydrophilicity and hydrophobicity are additionalconsiderations in choosing the pair of dead polymer and prepolymer forthe polymeric precursor mixture. Compatibility may generally be assumedin systems that appear clear or transparent upon mixing, although forthe purposes of this invention, compatibility is not required, but ismerely preferred, especially when transparent objects are to beproduced.

Even when only partial compatibility is observed at room temperature,the mixture often becomes uniform at a slightly increased temperature;i.e., many systems become clear at slightly elevated temperatures. Suchtemperatures may be slightly above ambient temperatures or may extend upto the vicinity of 100° C. or more. In such cases, because of the quickcuring time achieved by the process of this invention, the reactivecomponents can be quickly cured at the elevated temperature to “lock-in”the compatible phase-state in the cured resin before system cool-down.Thus, phase-morphology trapping can be used to produce an opticallyclear material instead of a translucent or opaque material that wouldotherwise form upon cooling.

The phase-morphology trapping is yet another advantage presented in thecurrent disclosure. The production of optically clear materialsnotwithstanding, virtually any thermoplastic may be used as the deadpolymer for the production of morphology-trapped materials.Thermoplastic polymers may be chosen in order to give optical clarity,high index of refraction, low birefringence, exceptional impactresistance, thermal stability, UV transparency or blocking, tear orpuncture resistance, desired levels or porosity, desired water contentupon equilibration in saline, selective permeability to desiredpermeants (high oxygen permeability, for example), resistance todeformation, low cost, or a combination of these and/or other propertiesin the finished object.

By way of example, thermoplastic polymers may include, but are notlimited to: polystyrene, polystyrene-co-methyl methacrylate,polystyrene-co-acrylonitrile, poly(α-methyl styrene), polymaleicanhydride, polystyrene-co-maleic anhydride, polymethyl(meth)acrylate,polybutyl(meth)acrylate, poly-iso-butyl (meth)acrylate,poly-2-butoxyethyl (meth)acrylate, poly-2-ethoxyethyl (meth)acrylate,poly(2-(2-ethoxy)ethoxy)ethyl (meth)acrylate, poly(2-hydroxyethyl(meth)acrylate), poly(hydroxypropyl (meth)acrylate), poly(cyclohexyl(meth)acrylate), poly(isobornyl (meth)acrylate), poly(2-ethylhexyl(meth)acrylate), polytetrahydrofurfuryl (meth)acrylate, polyethylene,polypropylene, polyisoprene, poly(1-butene), polyisobutylene,polybutadiene, poly(4-methyl-1-pentene), polyethylene-co-(meth)acrylicacid, polyethylene-co-vinyl acetate, polyethylene-co-vinyl alcohol,polyethylene-co-ethyl (meth)acrylate, polyvinyl acetate, polyvinylbutyral, polyvinyl butyrate, polyvinyl valerate, polyvinyl formal,polyethylene adipate, polyethylene azelate, polyoctadecene-co-maleicanhydride, poly(meth)acrylonitrile, polyacrylonitrile-co-butadiene,polyacrylonitrile-co-methyl (meth)acrylate,poly(acrylonitrile-butadiene-styrene), polychloroprene, polyvinylchloride, polyvinylidene chloride, polycarbonate, polysulfone,polyphosphine oxides, polyetherimide, nylon (6, 6/6, 6/9, 6/10, 6/12,11, and 12), poly(1,4-butylene adipate), polyhexafluoropropylene oxide,phenoxy resins, acetal resins, polyamide resins, poly(2,3-dihydrofuran),polydiphenoxyphosphazene, mono-, di-, tri-, tetra-, . . . polyethyleneglycol, mono-, di-, tri-, tetra-, . . . polypropylene glycol, mono-,di-, tri-, tetra-, . . . polyglycerol, polyvinyl alcohol, poly-2 or4-vinyl pyridine, poly-N-vinylpyrrolidone, poly-2-ethyl-2-ozazoline, thepoly-N-oxides of pyridine, pyrrole, imidazole, pyrazole, pyrazine,pyrimidine, pyridazine, piperadine, azolidine, and morpholine,polycaprolactone, poly(caprolactone)diol, poly(caprolactone)triol,poly(meth)acrylamide, poly(meth)acrylic acid, polygalacturonic acid,poly(t-butylaminoethyl (meth)acrylate), poly(dimethylaminoethyl(meth)acrylate), polyethyleneimine, polyimidazoline, polymethyl vinylether, polyethyl vinyl ether, polymethyl vinyl ether-co-maleicanhydride, cellulose, cellulose acetate, cellulose nitrate, methylcellulose, carboxy methyl cellulose, ethyl cellulose, ethyl hydroxyethylcellulose, hydroxybutyl cellulose, hydroxypropyl cellulose,hydroxypropyl methyl cellulose, starch, dextran, gelatin,polysaccharides/glucosides such as glucose and sucrose, polysorbate 80,zein, polydimethylsiloxane, polydimethylsilane, polydiethoxysiloxane,polydimethylsiloxane-comethylphenylsiloxane,polydimethylsiloxane-co-diphenylsiloxane, polymethylhydrosiloxane,poly(4-methylpentene-1), and cyclo-olefin copolymers such as ARTON® fromJSR, ZEONEX® and ZEONOR® from Nippon Zeon, and TOPAS® from Ticona. Theethoxylated and/or propoxylated versions of the above-mentioned polymersshall also be included under this disclosure as being suitable deadpolymers.

In one preferred embodiment, the polymeric precursor mixture comprises aprepolymer, a dead polymer, and optionally a reactive plasticizer and/ora non-reactive plasticizer which gives an optically clear homogeneousmolding upon cure. A preferable precursor mixture is a semi-solid.

One group of preferred dead polymers includes the polymers or copolymerscomprising sulfoxide, sulfide, and/or sulfone groups within or pendantto the polymer backbone structure. Gels containing these groups haveshown reduced protein adsorption in conventional contact lensformulations (see U.S. Pat. No. 6,107,365 and PCT Publ. No. WO00/02937).These polymers and copolymers are readily incorporated into thepolymeric precursor mixtures of the present invention.

Additionally preferred dead polymers are those containing one or morependant or terminal hydroxy groups. Examples of such polymers includepolyhydroxyethyl (meth)acrylate, polyhydroxypropyl (meth)acrylate,polyethylene glycol, cellulose, dextran, glucose, sucrose, polyvinylalcohol, polyethylene-co-vinyl alcohol, mono-, di-, tri-, tetra-, . . .polybisphenol A, and adducts of α-caprolactone with C₂₋₆ alkane diolsand triols. Copolymers, ethoxylated, and propoxylated versions of theabove-mentioned polymers are also preferred prepolymers.

Copolymers of these polymers with other monomers and materials suitablefor use as ophthalmic lens materials are also disclosed. Additionalmonomers used for copolymerization of the dead polymers may include, byway of example and without limitation, vinyl lactams such asN-vinyl-2-pyrrolidone, (meth)acrylamides such asN,N-dimethyl(meth)acrylamide and diacetone (meth)acrylamide, vinylacrylic acids such as (meth)acrylic acid, acrylates and methacrylatessuch as 2-ethylhexyl (meth)acrylate, cyclohexyl (meth)acrylate, methyl(meth)acrylate, isobornyl (meth)acrylate, ethoxyethyl (meth)acrylate,methoxyethyl (meth)acrylate, methoxy triethyleneglycol (meth)acrylate,hydroxytrimeththylene (meth)acrylate, glyceryl (meth)acrylate,dimethylamino ethyl(meth)acrylate and glycidyl (meth)acrylate, styrene,and monomers/backbone units containing quarternary ammonium salts.

The thermoplastics may optionally have small amounts of reactiveentities attached (copolymerized, grafted, or otherwise incorporated) tothe polymer backbone to promote crosslinking upon cure. They may beamorphous, semi-crystalline, or crystalline. They may be classified ashigh performance engineering thermoplastics (e.g., polyether imides,polysulfones, polyether ketones, etc.), or they may be biodegradable,naturally occurring polymers (starch, prolamine, and cellulose, forexample). They may be oligomeric or macromeric in nature. These examplesare not meant to limit the scope of compositions possible during thepractice of the current invention, but merely to illustrate the broadselection of thermoplastic chemistries permitted under the presentdisclosure.

In the present invention, the practice of morphology trapping is notlimited to homogeneous systems. Optically transparent phase-separatedsystems may also be beneficially prepared by including a phase-separatediso-refractive, prepolymer, prepolymer mixture, or a mixture of deadpolymers and prepolymers in the system. In that event, compatibility ofpolymeric components is not required. When a non-reactive diluent isadded which partitions itself approximately equally between the phases,a clear part results upon curing. Similarly, when a reactive plasticizeris added which either (1) partitions itself approximately equallybetween the phases or (2) has a refractive index upon polymerizingsimilar to that of the dead polymer mixture, a clear part also resultsupon curing. Alternatively, when the reactive plasticizer does notpartition itself equally between the phases and does not possess arefractive index upon curing similar to the polymer mixture, therefractive index of one of the phases may be altered by appropriatechoice of the polymer composition to give a resultant iso-refractivemixture. Such manipulations may be advantageously carried out inaccordance with the present invention in order to realizeheretofore-unattainable properties (i.e., simultaneous mechanical,optical, and processing properties) for a given material system.

With respect to the trapping of phase-separated morphology, onepreferred embodiment uses the phase-separated polymeric precursormixture comprising a prepolymer, a dead polymer, and optionally areactive plasticizer and/or a non-reactive plasticizer, which upon cureproduces a phase-separated iso-refractive molding. More preferably, theprecursor mixture is a semi-solid. Most preferably, the precursormixture is a semi-solid which has a high refractive index.

The phase-morphology trapping of the present invention is not restrictedto the optically clear systems. In fact, the invention is applicable tovirtually any morphologies which can be created in the polymericprecursor mixtures of this invention. Most polymer blends and blockcopolymers, and many other copolymers, result in phase-separatedsystems, providing an abundance of phase configurations to be exploitedby the materials designer. Polymer blends achieved by physically mixingtwo or more polymers are often used to elicit desirable mechanicalproperties in a given material system. For example, impact modifiers(usually lightly crosslinked particles or linear polymer chains) may beblended into various thermoplastics or thermoplastic elastomers toimprove the impart strength of the final cured resin. In practice, suchblends may be mechanical, latex, or solvent-cast blends; graft-typeblends (surface modification grafts, occasional grafts (IPNs,mechanochemical blends)), or block copolymers. Depending on the chemicalstructure, molecule size, and molecular architecture of the polymers,the blend may result in mixtures comprising both compatible andincompatible, amorphous, semi-crystalline or crystalline constituents.

The physical arrangement of the phase domains may be simple or complex,and may exhibit continuous, discrete/discontinuous, and/or bicontinuousmorphologies. Some of these are illustrated by the following examples:spheres of phase I dispersed in phase II; cylinders of phase I dispersedin phase II; interconnected cylinders; ordered bicontinuous,double-diamond interconnected cylinders of phase I in phase II (as havebeen documented for star-shaped block copolymers); alternating lamellae(well-known for di-block copolymers of nearly equal chain length); ringsforming nested spherical shells or spirals; phase within a phase withina phase (HIPS and ABS); and simultaneous multiples of these morphologiesresulting from the thermodynamics of phase separation (both nucleationand growth as well as spinodal decomposition mechanisms), kinetics ofphase separation, and methods of mixing, or combinations thereof.

Another category of materials utilizes “thermoplastic elastomers” as thedead polymer or prepolymer. An exemplary thermoplastic elastomer is atri-block copolymer of the general structure “A-B-A”, where A is athermoplastic rigid polymer (i.e., having a glass transition temperatureabove ambient) and B is an elastomeric (rubbery) polymer (glasstransition temperature below ambient). In the pure state, ABA forms amicrophase-separated or nanophase-separated morphology. This morphologyconsists of rigid glassy polymer regions (A) connected and surrounded byrubbery chains (B), or occlusions of the rubbery phase (B) surrounded bya glassy (A) continuous phase. Depending on the relative amounts of (A)and (B) in the polymer, the shape or configuration of the polymer chain(i.e., linear, branched, star-shaped, asymmetrical star-shaped, etc.),and the processing conditions used, alternating lamellae,semi-continuous rods, or other phase-domain structures may be observedin thermoplastic elastomer materials. Under certain compositional andprocessing conditions, the morphology is such that the relevant domainsize is smaller than the wavelength of visible light. Hence, parts madeof such ABA copolymers can be transparent or at worst translucent.Thermoplastic elastomers, without vulcanization, have rubber-likeproperties similar to those of conventional rubber vulcanizates, butflow as thermoplastics at temperatures above the glass transition pointof the glassy polymer region. Commercially important thermoplasticelastomers are exemplified by SBS, SIS, and SEBS, where S is polystyreneand B is polybutadiene, I is polyisoprene, and EB is ethylenebutylenecopolymer. Many other di-block or tri-block candidates are known, suchas poly(aromatic amide)siloxane, polyimide-siloxane, and polyurethanes.SBS and hydrogenated SBS (i.e., SEBS) are well-known products fromKraton Polymers Business (KRATON®). DuPont's LYCRA® is also a blockcopolymer.

When thermoplastic elastomers are chosen as the dead polymer forformulation, exceptionally impact-resistant yet clear parts may bemanufactured. The thermoplastic elastomers, by themselves, are notchemically crosslinked and require relatively high-temperatureprocessing steps for molding. Upon cooling, such temperaturefluctuations lead to dimensionally unstable, shrunken or warped parts.The prepolymers, if cured by themselves, may be chosen to form arelatively glassy, rigid network or a relatively soft, rubbery network,but with relatively low shrinkage in either case. When thermoplasticelastomers (i.e., dead polymers) and prepolymers are mixed together andreacted to form a cured resin, however, they form composite networkswith superior shock-absorbing and impact-resistant properties, whileexhibiting relatively little shrinkage during cure. By“impact-resistant” is meant resistance to fracture or shattering uponbeing struck by an incident object. Reactive plasticizers may also beincluded to promote crosslinking reaction and to achieve semi-solidconsistency. For the systems containing thermoplastic elastomers, theimpact strength may be increased further by compression molding theprecursor mixtures prior to curing.

Depending on the nature of the prepolymers, dead polymers, diluentsand/or reactive plasticizers used in the formulation, the final curedresin may be more flexible or less flexible (alternatively, harder orsofter) than the dead polymer. Composite articles exhibiting exceptionaltoughness may be fabricated by using a thermoplastic elastomer whichitself contains polymerizable groups along the polymer chain. Apreferred composition in this regard would be SBS tri-block orstar-shaped copolymers, for example, in which the reactive plasticizeris believed to crosslink lightly with the unsaturated groups in thebutadiene segments of the SBS polymer. The final cured moldings whichcontain these polymers also show good scratch resistance and solventresistance because the cured moldings comprise the crosslinked networkof prepolymers and dead polymers.

In one preferred embodiment of the present invention, the polymericprecursor mixture comprises a prepolymer, a thermoplastic elastomer, andoptionally a reactive plasticizer and/or a non-reactive diluent. Apreferred thermoplastic elastomer is the SBS copolymer.

A preferred formulation for developing optically clear and highlyimpact-resistant materials uses styrene-rich SBS tri-block copolymersthat contain up to about 75% styrene. These SBS copolymers arecommercially available from Kraton Polymers Business (KRATON®), PhillipsChemical Company (K-RESIN®), BASF (STYROLUX®), Fina Chemicals(FINACLEAR®), Asahi Chemical (ASAFLEX®), and others. In addition to highimpact resistance and good optical clarity, such styrene-rich copolymersyield material systems which exhibit other sometimes desirableproperties such as a relatively high refractive index (that is, an indexof refraction equal to or greater than about 1.54) and/or low density(with 30% or less of a reactive plasticizer, their densities are lessthan about 1.2 g/cc, and more typically about 1.0 g/cc).

In another embodiment of this invention, the precursor mixture is aphase-separated system comprising a prepolymer, a thermoplasticelastomer, and optionally a reactive plasticizer and/or a non-reactiveplasticizer which upon cure produces an optically clear phase-separatediso-refractive molding. More preferably, the precursor mixture is asemi-solid. Most preferably, the precursor mixture is a semi-solid whichhas a high refractive index.

When the mixture refractive index is an especially importantconsideration, high refractive index polymers may be used as one or moreof the dead-polymer components. Examples of such polymers includepolycarbonates and halogenated and/or sulfonated polycarbonates,polystyrenes and halogenated and/or sulfonated polystyrenes,polystyrene-polybutadiene block copolymers and their hydrogenated,sulfonated, and/or halogenated versions (all of which may be linear,branched, star-shaped, or non-symmetrically branched or star-shaped,etc.), polystyrene-polyisoprene block copolymers and their hydrogenated,sulfonated and/or halogenated versions (including the linear, branched,star-shaped, and nonsymmetrical branched and star-shaped variations,etc.), polyethylene or polybutylene terephthalates (or other variationsthereof), poly(pentabromophenyl (meth)acrylate), polyvinyl carbazole,polyvinyl naphthalene, poly vinyl biphenyl, polynaphthyl (meth)acrylate,polyvinyl thiophene, polysulfones, polyphenylene sulfides or oxides,polyphosphine oxides or phosphine oxide-containing polyethers, urea-,phenol-, or naphthyl-formaldehyde resins, polyvinyl phenol, chlorinatedor brominated polystyrenes, poly(phenyl α- or β-bromoacrylate),polyvinylidene chloride or bromide, and the like.

As stated previously, increasing the aromatic content, the halogencontent (especially bromine), and/or the sulfur content are generallyeffective means well known in the art for increasing the refractiveindex of a polymeric material. High index, low density, and resistanceto impact are properties especially preferred for ophthalmic lenses asthey enable the production of ultra thin, lightweight eyeglass lenses,which are desirable for low-profile appearances and comfort and safetyof the wearer.

Alternatively, elastomers, thermosets (e.g., epoxies, melamines,acrylated epoxies, acrylated urethanes, etc., in their uncured state),and other non-thermoplastic polymeric compositions may be desirablyutilized as the dead polymers during the practice of this invention.

One embodiment of the process of the present invention consists of threesteps: 1) polymerization, 2) functionalization or derivatization, and 3)molding and curing. Polymeric precursor mixtures are produced by thecontinuous process which comprises polymerization and functionalizationor derivatization steps. The continuous process of this invention iseconomical because it eliminates the costly steps of isolation andrecovery of prepolymers. The present process also eliminates the mixingof prepolymers with dead polymers, non-reactive plasticizers, and/orreactive plasticizers, which often has to be carried out at hightemperatures where the degradation of polymers becomes a problem.

In the polymerization step, the polymerization catalyst can be a thermalinitiator which generates free radicals at moderately elevatedtemperatures. Thermal initiators such as lauryl peroxide, benzoylperoxide, dicumyl peroxide, t-butyl hydroperoxide,azobisisobutyronitrile (AIBN), potassium or ammonium persulfate, forexample, are well known and are available from chemical suppliers suchas Aldrich. Photoinitiators may be used in place of or in combinationwith one or more thermal initiators so that the polymerization reactionmay be triggered by a source of actinic or ionic radiation.Photoinitiators such as the Irgacure® and Darocur® series are well-knownand commercially available from Ciba Geigy, as is the Esacure® seriesfrom Sartomer. Examples of photoinitiator systems arebis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide, benzoinmethyl ether, 1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenylpropane-1-one (sold under the TradenameDAROCUR 1173 by Ciba Specialty Chemicals), and 4,4′-azobis(4-cyanovaleric acid), available from Aldrich Chemicals. For a reference oninitiators, see, for example, Polymer Handbook, J. Brandrup, E. H.Immergut, eds., 3rd Ed., Wiley, New York, 1989.

Polymerization may be carried out using solvents and/or in the presenceof non-reactive diluents which constitute the final precursor mixtures.Solvents are removed after the functionalization or derivatization step.Preferred solvents are volatile solvents which can be readily removed byevaporation or vacuum distillation. If the precursor mixtures forisometric casting are desired, the amount of non-reactive diluents isadjusted such that the moldings exhibit little net change in the volumeafter equilibration in physiological salt solutions.

Solvents may be advantageously used to decrease the viscosity of thereaction medium, which provides a good mixing of solution. The reductionof solution viscosity also avoids the mixing at elevated temperaturesand/or with high shearing, which often degrades polymers. In addition,for the monomer mixtures that contain multifunctional monomers, thepresence of solvents eliminates or minimizes the formation of insolublegels during the polymerization reaction by decreasing the monomerconcentration. Volatile solvents also assist the removal of residualimpurities by evaporation or vacuum distillation after thefunctionalization step.

Purification of the polymer at any stage of the process, i.e., eitherbefore or after functionalization, can be achieved by conventionalmethods, examples of which are evaporation, vacuum distillation, andvacuum drying. Purification can also be achieved by filtration,including microfiltration to remove particulates and ultrafiltration toremove material below a particular molecular weight that is determinedby the selection of the utlrafiltration membrane.

An example of an ultrafiltration process is that disclosed in U.S. Pat.No. 6,072,020 (Arcella et al., Jun. 6, 2000), incorporated herein byreference. According to such a process, the polymer afterfunctionalization and still dissolved in the solvent in whichfunctionalization has been performed is filtered by semi-permeablemembranes with pores in the range of 0.05 micron to 0.5 micron, followedby a second stage filtration using membranes with pores with a molecularweight limit of 5-500 kDa. The second stage filtration is performedunder a gradient of a second volatile solvent such as ethanol ormethanol. Displacement of all of the first solvent by the second solventmay involve six volumes of the second solvent relative to the initialvolume of the first solvent. The non-aqueous diluent can then be addedand the solvent removed by reduced pressure evaporation to give thecomposition ready for casting and curing.

In the present invention, the dead polymers may also be added to thereaction medium at a desired time before, during, and/or after thepolymerization reaction, and/or after the functionalization reaction. Asstated previously, the dead polymers may be advantageously utilized toproduce desired morphologies, which depend on the components andcompositions of the reaction formulations as well as on the processingconditions such as temperatures, pressures, and mixing conditions. Thecompositions of reaction media change as the reaction proceeds. Thus, inthe process of this invention, the desired morphologies of polymericprecursor mixtures may be obtained by manipulating the time of additionof dead polymers to the reaction media, which is yet another advantagepresented in the current disclosure.

After the polymerization reaction, polymers are functionalized withreactive groups to give prepolymers. The reaction chemistry offunctionalization depends on the type of functionalizable groups on thepolymer backbone and the reaction condition is chosen accordingly. Forexample, the functionalization reaction of hydroxyls by methacrylicanhydride proceeds spontaneously at room temperature without using acatalyst.

The process of the present invention is particularly useful forproducing the semi-solid precursor mixtures which contain thermallysensitive polymers such as the high-refractive index polymers forophthalmic lenses comprising sulfurs and/or halogens. When semi-solidprecursor mixtures are obtained by blending prepolymers and reactiveplasticizers, mixing often has to be carried out at high temperatures(e.g., above 250° C.) where the degradation of polymers becomes aproblem. In the present invention, the semi-solid precursor mixtures areobtained at moderate temperatures, preferably at temperatures below 150°C. and more preferably below 100° C.

Upon completing the functionalization or derivatization reaction, aninitiator or polymerization catalyst is also typically added into thepolymeric precursor mixture in order to facilitate curing upon exposureof the precursor mixture to a source of polymerizing energy such aslight or heat. Optionally, other additives may be included in theprecursor mixtures such as mold release agents, preservative agents,pigments, dyes including photochromic dyes, organic or inorganic fibrousor particulate reinforcing or extending fillers, thixotropic agents,indicators, inhibitors or stabilizers (weathering or non-yellowingagents), UV absorbers, surfactants, flow aids, chain transfer agents,foaming agents, porosity modifiers, and the like. The initiator andother optional additives may be dissolved or dispersed in the reactiveplasticizer and/or diluent component prior to combining with the deadpolymer and/or prepolymer to facilitate complete dissolution into anduniform mixing with the polymeric component(s).

For the production of ophthalmic moldings, the crucial criteria indetermining whether a polymeric precursor mixture can be employed in thenovel process of the present invention are that the precursor mixturemust be homogeneous to a sufficient degree allowing for optical clarityupon cure; that the mixture be capable of undergoing a polymerizationreaction upon the application of light, heat, or some other form ofpolymerizing energy or polymerization-triggering mechanism; and, forsemi-solid precursors, that the mixture exhibit a semi-solid consistencyduring at least one part of the manufacturing process used to producethe molding of interest.

The semi-solid precursor materials of the present invention may beadvantageously molded by several different molding techniques well-knownand commonly practiced in the art. For example, static castingtechniques, where the molding material is placed between two mold halveswhich are then closed to define an internal cavity which in turn definesthe molding shape to be produced, are well-known in the field ofophthalmic lens production. See, for example, U.S. Pat. Nos. 4,113,224,4,197,266, and 4,347,198. Likewise, compression molding techniques wheretwo mold halves are again brought together, but not necessarily broughtinto contact with one another, to define one or more molded surfaces,are well-known in the field of thermoplastic molding. Injection moldingis another technique that may be adapted for use with the presentsemi-solid precursor materials of the present invention, where thesemi-solid material can be rapidly forced into a cavity defined by twotemperature-controlled mold halves, the material being optionally curedwhile in the mold, then being ejected from the mold halves with asubsequent shaping and or curing step if needed (if the semi-solid isnot cured or only partially cured in the injection molding machine).

Such processes without curing or with only partial curing in the moldare suitable for the production of preforms as long as the preformsmaintain semi-solid consistency. The preforms may take the form ofslabs, disks, balls, or sheets, for example, which can be later used ina static casting or compression molding process with curing tomanufacture the final objects of interest. For the production ofophthalmic lenses, static casting, compression, and injection moldingare all preferred processes because of their current prevalence in theart with either unreactive thermoplastic materials (injection andcompression molding) or reactive precursors in a liquid state (staticcasting).

The following examples are offered as illustration and are not intendedto limit the scope of the invention.

EXAMPLE 1

A temperature-controlled 250-mL four-neck flask equipped with athermometer, condenser, and nitrogen inlet was charged with 10 g ofpolyethylene glycol having an average molecular weight of 400 (PEG 400,Aldrich) as a non-reactive non-volatile diluent and 20 g of acetone as avolatile solvent. The mixture was stirred for a few minutes beforeadding 10 g of 2-hydroxyethyl methacrylate (HEMA), 0.15 g of methacrylicacid (MAA), and 12 mg of azobisisobutyronitrile (AIBN) as an initiator.The mixture was then purged with purified nitrogen while stirring forapproximately 15 minutes.

The solution was slowly heated to and maintained at 60° C. for 2 hoursto carry out polymerization. After polymerization, a clear and highlyviscous liquid, semi-solid, or hydrogel was formed. The mixture was thencooled down to room temperature and 0.21 g of methacrylic anhydride (MA)was injected as a functionalizing agent. The reaction between thehydroxyl of HEMA and MA proceeds spontaneously at room temperaturewithout using a catalyst. The solution was stirred for 12 hours to carryout the functionalization reaction in which the reactive methacrylicgroups were introduced on the polymer backbone. Upon the completion offunctionalization reaction, volatile acetone and residual impuritieswere removed by evaporation or vacuum distillation to give a polymericprecursor mixture comprising PEG 400 and methacrylate-functionalizedpHEMA-co-MAA copolymer. The resulting material was a highly viscousliquid, semi-solid, or hydrogel.

In this example, the concentration of acetone in the reaction mixturecan be varied from 10 wt % to 80 wt %. When the acetone concentrationwas higher than 80 wt %, the pHEMA-co-MAA copolymer precipitated duringpolymerization. When the acetone concentration was below 10 wt %,significant gellation occurred. The gellation is caused by thecrosslinking of copolymer due to the small amount of difunctionalmonomer present in HEMA as impurities. The properties of the precursormixtures can be varied by variations in the choice of solvent, solventconcentration, reaction time, reaction temperature, and concentration ofdiluents.

The degree of functionalization can be readily varied by adjusting theamount of MA added to the reaction mixture as a functionalizing agent.While keeping the amounts of HEMA and MAA unchanged, variouspHEMA-co-MAA copolymers with functionalities from 0.3 to 5% have alsobeen synthesized according to the procedure described above by adjustingthe amount of MA. Using suitable substituting agents, other types ofreactive groups (e.g., acrylate and methacrylamide) may also beintroduced to the backbone of pHEMA-co-MAA.

EXAMPLE 2

A reaction vessel identical to that of Example 1 was charged with 15 gof PEG 400 and 18 g of acetone. The mixture was stirred for a fewminutes before adding 15 g of HEMA, 0.21 g of MAA, and 15 mg of AIBN.The mixture was then purged with nitrogen while stirring forapproximately 15 minutes. Next, the solution was slowly heated to andmaintained at 60° C. for 3 hours to carry out polymerization. Becausethe viscosity of reaction medium increases during polymerization, it maybe advantageous to add more solvent to the reaction medium duringpolymerization to ensure the completion of the reaction and to reducethe crosslinking of copolymer. In this example, 10 g of acetone wasfurther added to the reaction mixture after one hour from the start ofpolymerization reaction and additional 10 g of acetone was also added tothe solution after 2 hours from the start of polymerization.

After polymerization, the reaction mixture was cooled down to roomtemperature and 0.32 mL of MA was added. The solution was kept undervigorous stirring for 12 hours to carry out the functionalizationreaction. Finally, volatile acetone and residual impurities were removedby vacuum distillation.

EXAMPLE 3

A copolymer pHEMA-co-MAA was synthesized according to the proceduredescribed in Example 1. After polymerization, 0.18 g of glycidylmethacrylate was injected as a functionalizing agent into the reactionmixture and the functionalization reaction was carried out at roomtemperature for 24 hours under vigorous stirring. The volatile solventand residual impurities were then removed by vacuum distillation. Theresulting precursor mixture was a clear semi-solid that is suitable forbiomedical products and devices which require minimum purification stepprior to their intended use.

EXAMPLE 4

The reaction vessel was charged with 10 g of PEG 400 and 20 g ofacetone. The mixture was stirred for a few minutes before adding 10 g ofHEMA, 0.15 g of MAA, and 10 mg of AIBN. Subsequently, the reactionmixture was purged with purified nitrogen while stirring forapproximately 15 minutes. The solution was then slowly heated to andmaintained at 60° C. for 2 hours to carry out polymerization. Afterpolymerization, a clear mixture was obtained which was a highly viscousliquid, semi-solid, or hydrogel. The mixture was cooled down to roomtemperature and 0.21 g of MA was injected. The solution was stirred for12 hours to carry out the functionalization reaction by introducingreactive methacrylic groups to the copolymer backbone. Upon completingthe functionalization reaction, a photoinitiator such as IRGACURE 184,DAROCUR 1173, or IRGACURE 1750 was mixed with the solution at 1 wt %with respect to the total monomer content. Finally, volatile acetone andresidual impurities were removed by vacuum distillation.

Depending on the reaction conditions, the resulting precursor mixturewas a highly viscous liquid, semisolid, or hydrogel containing aphotoinitiator. The precursor mixture obtained in this example is readyfor molding and curing without mixing further with an initiator.

EXAMPLE 5

A procedure similar to that used in Examples 1 to 4 was used tosynthesize pHEMA or pHEMA-co-MAA using different solvents. The componentand composition of other constituents of the reaction mixture remainedunchanged. Instead of acetone, methyl ethyl ketone (MEK),tetrahydrofuran (THF), or a combination of both was added to thereaction mixture as a volatile solvent. The advantage of using MEK orTHF over acetone is that because these solvents have relatively higherboiling points, polymerization can be carried out at temperatures around70° C. which cannot be achieved with the more volatile acetone. MEK andTHF are still volatile enough however to be readily removed byevaporation or vacuum distillation. Polymerization reactions,particularly free radical polymerizations, proceed faster and closer tocompletion at higher temperatures. For the pHEMA and pHEMA-co-MAAsynthesized in this example, the disadvantage is that these polymershave lower solubility in MEK and THF than in acetone. To prevent theprecipitation of the copolymers, the concentration of MEK or THF shouldbe kept below 50-60%, preferably below 50%, with respect to the totalamount of reaction mixture.

EXAMPLE 6

A reaction vessel identical to that of Example 1 was charged with 10 gof PEG 400 and 40 g of ethanol. The mixture was stirred for a fewminutes before adding 10 g of HEMA, 0.15 g of MAA, and 10 mg of AIBN.Subsequently, the mixture was purged with nitrogen while stirring forapproximately 15 minutes. The solution was then slowly heated to andmaintained at 60° C. to carry out polymerization for 2.5 hours. Becauseethanol is a better solvent for the copolymer synthesized here thanacetone, using ethanol as a solvent, the amount of solvent in thereaction mixture can be increased to decrease the monomer concentrationbelow the lowest monomer concentration achievable with the use ofacetone as a solvent. After polymerization, a clear and viscous liquidwas obtained.

The hydroxy group of ethanol, however, may preferably reacts with MAused as a functionalizing agent in the following functionalization step.To minimize the side reaction between ethanol and MA, ethanol wasremoved under vacuum and one or more of non-aqueous solvents, such asacetone, THF, and MEK were added to the mixture containing pHEMA-co-MAAcopolymer and PEG 400.

The copolymer was functionalized by adding 0.32 g of MA to the solution.The mixture was stirred vigorously for 12 hours at room temperature.After the functionalization reaction is completed, volatile solvents andresidual impurities were removed by vacuum distillation.

The resulting precursor mixture is a highly viscous liquid, semi-solid,or hydrogel. Compared to the copolymers synthesized in Examples 1 to 4,the copolymer synthesized in this example is less crosslinked because alower monomer concentration was used during the polymerization reaction.

EXAMPLE 7

A reaction vessel identical to that of Example 1 was charged with 10 gof PEG 400 and 20 g of acetone. The mixture was stirred for a fewminutes before adding 8 g of HEMA, 1.5 g of N-vinyl-2-pyrrolidone, 0.5 gof MAA, and 10 mg of AIBN. Subsequently, the mixture was purged withnitrogen while stirring for approximately 15 minutes. The solution wasthen slowly heated to and maintained at 60° C. to carry outpolymerization for approximately 3 hours. After polymerization, themixtures was clear and a semi-solid or hydrogel was obtained. Themixture was cooled down to room temperature and 0.55 g of MA wasinjected. The solution was then stirred for 12 hours to carry out thefunctionalization reaction by introducing reactive methacrylic groups onthe copolymer backbone. Upon completing the functionalization reaction,volatile acetone and residual impurities were removed by vacuumdistillation.

The resulting precursor mixture was a highly viscous liquid, semi-solid,or hydrogel. The prepolymer synthesized in this example has a relativelyhigh degree of functionalization and therefore will crosslink upon curemore than the prepolymers synthesized in the previous examples.

EXAMPLE 8

This example describes the molding and curing process to produce contactlenses. The precursor mixture comprises 50 wt % of 0.75% functionalizedpHEMA-co-MAA and 50 wt % of PEG 400. 0.1 Gram of this precursor mixturewas first mixed with 0.002 g of IRGACURE 184 (a photoinitiator) by handbetween two glass plates for a few minutes. For the precursor mixtureswhich already contain photoinitiators, it is not necessary to mix theprecursor mixture with a photoinitiator prior to molding.

Approximately 0.08 g of the resulting material was then placed betweentwo contact lens molds made of polystyrene. The assembly was placed on apress at 50° C. with slight pressure to controllably bring the moldsinto contact with each other around their periphery. Excess material wassqueezed out of the mold as the two molds came together, and the amountof overflow was determined by the amount of material originally placedinto the mold versus the mold cavity volume. For the molds made ofpolystyrene, higher molding temperatures up to about 80° C. may beutilized without deforming the molds.

The molding procedure described above was found to squeeze out the airbubbles which are occasionally trapped in the precursor mixtures whenthe mixtures are manually transferred to the molds. It is desirablehowever to completely eliminate air bubbles from the precursor mixturesbefore closing the molds. One approach to remove air bubbles from theprecursor mixtures in the molds is to place the material in a rearcontact lens mold and apply a slight vacuum on the mold forapproximately 10 minutes. Alternatively, the material may be left in arear mold for several hours to one day, during which the precursormixture slowly settles down and the air bubbles often come out from theprecursor mixture spontaneously without applying a vacuum, or many smallair bubbles coalesce into a few large bubbles which are readily squeezedout by simply closing the molds. These two approaches are quiteeffective in removing the trapped air bubbles from the precursormixtures in the molds. The latter approach, however, may not beeffective for highly viscous semi-solid precursor mixtures.

Once the molds were pressed together, the ophthalmic molding was curedfor approximately 20 seconds under a Fusion UV light source using theD-, H-, or V-bulb. For a given photoinitiator, the type of light bulb ischosen accordingly to achieve the optimum absorption of light by thephotoinitiator. It should be noted that shorter curing times arepossible, and 20 seconds serves as an upper limit for the amount of timerequired to cure this particular molding composition and geometry. Themold assembly was then removed from the UV lamp, and the overflowmaterial was trimmed from the edge of the lens molds. The lens moldswere opened after allowing them to cool to room temperature, and anophthalmic contact lens was thus obtained.

The ophthalmic lens of the present example contains an equilibrium watercontent of approximately 50-60%, which depends on the copolymercomposition, degree of functionality of the copolymer which determinesthe crosslinking density of cured lens. Polymers functionalized at about0.5 to 1% exhibited mechanical moduli similar to those seen forcommercial contact lens materials having similar water contents, andwere able to stretch to 2-4 times their original length before breaking.

The molding and curing procedure described in this example is a generalprocedure which may be applicable to any precursor mixtures for contactlenses obtained by the present invention.

EXAMPLE 9

In a slightly different molding and curing process from the processdescribed in Example 8, a visible light initiator4,4′-azobis(4-cyanovaleric acid) was mixed with the precursor mixturesof Examples 1 to 3 at 1 wt %. The ophthalmic molds containing theprecursor mixtures were prepared according to the procedure described inExample 8 and were cured by a high intensity illumination source(Fiber-Lite Ringlight System, Dolan-Jenner) for 20 minutes. Curing timescan be shortened by using more intense visible light sources.

EXAMPLE 10

0.08 Gram of the precursor mixture from Example 4 was placed in a pairof contact lens molds. The mixing with initiator was not necessary forthis precursor mixture because a photoinitiator had been alreadydissolved in the mixture during the preparation of precursor mixture.The lens molds were closed by the procedure described in Example 8 andthe mold assembly was cured by a diffuse UV light source (Blak-Ray 100AP, UVP, Inc.) for 10 minutes. Curing times can be shortened by usingmore intense UV light sources.

The cured lens was removed from the molds and was hydrated in a bufferedsaline solution. The equilibrium water content was 54%, and the samplelens had an elongation to break of approximately 250%.

EXAMPLE 11

The number and amount of diluents may be chosen according to therequirements and desired properties. In particular, the number andamount of diluents may be adjusted to achieve isometric exchange betweenthe diluents and physiological saline solution. The easiest approach isto add the desired amount of diluents in the polymerization step. Inrare occasions, the diluents may be adjusted before the molding process.

As an example, 0.1 g. of isopropanol and 0.15 g. of alkoxylatedglucosides were mixed 0.167 g. of material synthesized according toExample 5. The mixture was then placed in a rear contact lens mold anddegassed for 5 minutes. Subsequently, the mold assembly was pressedslightly and UV cured for 20 seconds.

In general a contact lens thus obtained has essentially the exact shapeand diameter as the contact lens mold since the molding materialcontains the amount of diluent which is the same as the equilibriumwater amount once the lens is immersed in the physiological salinesolution. Consequently, a isometric exchange of diluents and water isachieved.

EXAMPLE 12

A clear solution consisting of 1 mL of PEG 400, 33 mL of acetone, 1 mLof HEMA and 0.21 mL of MA was prepared. To the mixture were added 1.5mg. of Blue HEMA, 50 mg. of UV block N7966 and 12 mg. of AIBN. Themixture was stirred under nitrogen purge for approximately 15 minutes.Subsequently, the temperature was raised to 58° C. and the monomers werepolymerized for 90 minutes. After the polymerization, a clear, bluishconcentrated polymer solution or semi-solid was formed. To introduce thereactive sites, 0.35 mL of methacrylic anhydride was injected after theconcentrated solution or gel was cooled down to room temperature. Themixture was stirred for 12 hours for derivatization. Finally, thevolatile solvent and residual impurities were removed by vacuumdistillation.

The resulting material was used in making contact lenses, intraocularlenses and biomedical devices.

EXAMPLE 13

For ophthalmic lenses which have high refractive indices, the semi-solidprecursor mixtures are obtained from the prepolymers comprisinghigh-refractive index monomers. As an example, the starting monomermixture comprises chlorostyrene, a high-refractive index monomer, and3-phenoxy-2-hydroxypropyl methacrylate which contains a functionalizablehydroxyl. Another example of monomer mixture comprises bromostyrene, ahigh-refractive index monomer, and3-(2,4-dibromo-3-methylphenoxy)-2-hydroxypropyl (meth)acrylate whichalso gives high-refractive index and has a functionalizable hydroxyl.

Upon completing the polymerization reaction in a suitable solvent,methacrylic anhydride is added to the polymer solution to carry outfunctionalization to obtain the prepolymers functionalized with reactivemethacrylate groups. Next, reactive plasticizers and photoinitiators areadded to the prepolymer solution. The types and relative amounts ofreactive plasticizers are selected accordingly to obtain desiredproperties of precursor mixtures and cured articles such as semi-solidconsistency, high-impact strength, and high-refractive index, whilemaintaining optical clarity. Solvents are then removed to givesemi-solid precursor mixtures for high-refractive index ophthalmiclenses which can be cured rapidly by UV.

EXAMPLE 14

Semi-solid precursor mixtures suitable for ophthalmic lenses are alsoproduced from phase-separated iso-refractive systems using styrene-richSBS block copolymers as dead polymers which show good impact strength.Commercially available styrene-rich SBS block copolymers such as KRATON®from Kraton Polymers Business and K-RESIN® from Phillips ChemicalCompany have refractive indices of about 1.57. Examples of prepolymerswhich are incompatible with SBS block copolymers are functionalizedversions of styrene-methyl methacrylate (SMMA) copolymers,styrene-acrylonitrile (SAN) copolymers, and styrene-maleic anhydride(SMA) copolymers in which the copolymer compositions are adjusted suchthat the refractive indices of prepolymers match the refractive index ofSBS block copolymer at room temperature. SMMA and SAN copolymers arealso copolymerized with the monomers which contain functionalizablegroups. The anhydride group of SMA can be functionalized with suitablefunctionalizing agents such as those containing hydroxyls.

As an example, a copolymer is synthesized from a monomer mixturecomprising styrene, methyl methacrylate, and 2-hydroxyethyl methacrylate(HEMA) in a suitable solvent. The polymerization may be carried out inthe presence of SBS block copolymers as dead polymers. If desired, deadpolymers are mixed with the prepolymer solution after completingfunctionalization. The resulting morphologies may depend on the time ofaddition of dead polymers to the reaction mixture.

Hydroxyls of HEMA are functionalized with reactive methacrylate groupsusing methacrylic anhydride as a functionalizing agent. Upon completingfunctionalization, reactive plasticizers and photoinitiators are addedto the reaction mixture. The types and relative amounts of reactiveplasticizers are chosen accordingly to achieve desired semi-solidconsistency without losing optical clarity. For the mixtures of SBSblock copolymer and SMMA copolymer, examples of reactive plasticizersinclude ethoxylated bisphenol A di(meth)acrylates and benzyl(meth)acrylate.

Solvent is then removed from the mixture to give a phase-separatediso-refractive semi-solid precursor mixture. For the systems containingSBS block copolymers, the impact strength of cured articles can beincreased further by performing compression molding on the semi-solidprecursor mixtures prior to cure. Thus, compression-molded preforms maybe advantageously obtained for the semi-solid precursor mixtures whichcontain SBS block copolymers. These preforms are used later for themanufacture of final objects of interest such as ophthalmic lenses whichhave relatively high refractive indices and good impact strength.

EXAMPLE 15

This example illustrates the preparation of a copolymer of2-hydroxyethyl methacrylate, methacrylic acid, and blue HEMA, usingethanol as a solvent for the polymerization reaction.

A 1000-mL four-neck flask, equipped with a thermometer, condenser,nitrogen inlet, and thermocouple, was charged with 53.65 g of2-hydroxyethyl methacrylate (HEMA), 1.07 g of methacrylic acid (MAA), 6mg of blue HEMA, and 500 mL of ethanol. The mixture was purged with highpurity nitrogen gas and stirred for approximately 15 min. Subsequently,0.82 g of azobisisobutyronitrile (AIBN) was added and the solution wasstirred until the AIBN dissolved. Polymerization was conducted byheating the solution to 70° C. and maintaining that temperature for 5hours.

After the completion of polymerization, the solution was allowed to coolto room temperature. The solution was then transferred to a funnel andslowly dropped into 3000 mL of stirred hexane. A bluish solid copolymerprecipitated and was collected by filtration, then placed in a vacuumoven for 24 hours, leaving a dry solid. The yield of dried solid was90%.

EXAMPLE 16

This example illustrates the functionalization of the copolymer preparedin Example 15 with methacrylic anhydride, using pyridine as a solventfor the functionalization reaction.

Under an inert atmosphere, a 250-mL round-bottom flask equipped withstir bar and septum was charged with 5.29 g of poly(HEMA-co-MAA)synthesized according to Example 15. Anhydrous pyridine (50 mL) wasadded and the mixture was stirred until the polymer had completelydissolved. Methacrylic anhydride (94 mg) was then added and theresulting mixture was allowed to stir at ambient temperature overnight.The resulting solution of poly(HEMA-co-MAA) functionalized withmethacrylic anhydride was then slowly poured into a beaker containing450 mL of vigorously stirred hexanes causing precipitation of thefunctionalized copolymer as a sticky viscous oil. The product soobtained was allowed to redissolve with stirring in 100 mL ethanol andthen re-precipitated as a well dispersed solid by slow addition to 550mL of vigorously stirred hexanes. Decantation and washing of the solidswith two additional portions of hexanes, followed by drying in vacuogave 4.57 g of free-flowing light blue powder.

EXAMPLE 17

This example illustrates the further processing of the functionalizedcopolymer prepared in Example 16 to prepare the copolymer forcrosslinking in a mold, using methanol to facilitate the dissolving ofthe copolymer and the transfer of the copolymer to the mold.

The functionalized copolymer prepared in Example 16 (0.6 gram) wascombined with PEG 400 (0.9 g), and IRGACURE 184 (0.006 g) in a methanol(2 g) solution. Approximately 0.2 g of the solution was placed in afront mold half which was then placed in a vacuum oven to remove themethanol. The result was a viscous or semi-solid composition ready forfinal molding and curing.

The foregoing is offered primarily for purposes of illustration. Furthervariations and substitutions that are still within the scope of thisinvention will be readily apparent to those skilled in the art.

1. A process for the manufacture of a molded hydrogel, said processcomprising: (a) casting a composition comprising (i) a crosslinkablenon-water-soluble polymer which when crosslinked by a crosslinkingreaction and saturated with water forms a hydrogel containing apredetermined volumetric proportion of water, and (ii) a non-aqueousdiluent that is inert to said crosslinking reaction, said non-aqueousdiluent being in a volumetric proportion substantially equal to saidpredetermined volumetric proportion of water in said hydrogel,  in amold under conditions causing conversion of said composition to anon-aqueous gel by crosslinking said crosslinkable non-water-solublepolymer; and (b) substituting an aqueous liquid for said non-aqueousdiluent in said nonaqueous gel to form said hydrogel.
 2. A process inaccordance with claim 1 in which said composition is a semi-solid.
 3. Aprocess in accordance with claim 1 in which said composition is aviscous liquid.
 4. A process in accordance with claim 1 in which saidaqueous liquid is an aqueous physiological saline solution.
 5. A processin accordance with claim 1 further comprising (A) forming saidcrosslinkable non-water-soluble polymer by coupling a functionalizingagent to a non-water-soluble precursor polymer, said functionalizingagent defined as an agent that when so coupled is capable of undergoinga crosslinking reaction.
 6. A process in accordance with claim 5 inwhich step (A) comprises coupling said functionalizing agent to saidnon-water-soluble precursor polymer in said non-aqueous diluent to formsaid composition.
 7. A process in accordance with claim 5 in which step(A) comprises (A.1) coupling said functionalizing agent to saidnon-water-soluble precursor polymer to form said crosslinkablenon-water-soluble polymer, and (A.2) combining said crosslinkablenon-water-soluble polymer with said non-aqueous diluent, subsequent tosaid coupling, to form said composition.
 8. A process in accordance withclaim 1 in which said composition further comprises a dead polymer.
 9. Aprocess in accordance with claim 5 in which said composition furthercomprises a dead polymer, and step (A) comprises (A.1) coupling saidfunctionalizing agent to said non-water-soluble precursor polymer toform said crosslinkable non-water-soluble polymer, and (A.2) combiningsaid crosslinkable non-water-soluble polymer with said non-aqueousdiluent and said dead polymer, subsequent to said coupling, to form saidcomposition.
 10. A process in accordance with claim 1 in which saidcomposition further comprises a reactive plasticizer.
 11. A process inaccordance with claim 5 in which said semi-solid composition furthercomprises a reactive plasticizer, and step (A) comprises (A.1) couplingsaid functionalizing agent to said non-water-soluble precursor polymerto form said crosslinkable non-water-soluble polymer, and (A.2)combining said crosslinkable non-water-soluble polymer with saidnon-aqueous diluent and said reactive plasticizer, subsequent to saidcoupling, to form said composition.
 12. A process in accordance withclaim 1 in which said composition further comprises a dead polymer and areactive plasticizer.
 13. A process in accordance with claim 5 in whichsaid composition further comprises a dead polymer and a reactiveplasticizer, and step (i) comprises (i.1) coupling said functionalizingagent to said non-water-soluble precursor polymer to form saidcrosslinkable non-water-soluble polymer, and (i.2) combining saidcrosslinkable non-water-soluble polymer with said non-aqueous diluent,said dead polymer, and said reactive plasticizer, subsequent to saidcoupling, to form said composition.
 14. A process in accordance withclaim 5 in which said non-water-soluble precursor polymer contains aplurality of sites capable of coupling to said functionalizing agent,and step (i) comprises coupling said functionalizing agent to about 0.2%to about 5% of said sites.
 15. A process in accordance with claim 14 inwhich said sites consist of reactive groups selected from the groupconsisting of hydroxyl, amino, carboxylate, thiol, disulfide, anhydride,urethane, and epoxide groups.
 16. A process in accordance with claim 15in which said reactive group is a hydroxyl group.
 17. A process inaccordance with claim 16 in which said functionalizing agent is a memberselected from the group consisting of epoxides, oxiranes,carbonyldiimidazoles, periodates, acid halides, alkyl halides,isocyanates, halohydrins, and anhydrides.
 18. A process in accordancewith claim 17 in which said functionalizing agent is an anhydride.
 19. Aprocess in accordance with claim 5 in which said non-water-solubleprecursor polymer is a polymer of monomers selected from the groupconsisting of hydroxyethyl acrylate, hydroxyethyl methacrylate,hydroxypropyl acrylate, and hydroxypropyl methacrylate.
 20. A process inaccordance with claim 5 in which said non-water-soluble precursorpolymer is a polymer of monomers comprising hydroxyethyl methacrylate.21. A process in accordance with claim 5 in which said non-water-solubleprecursor polymer is a copolymer of hydroxyethyl methacrylate, bluehydroxyethylmethacrylate, and methacrylic acid.
 22. A process inaccordance with claim 1 in which said crosslinkable non-water-solublepolymer is a product of (1) a polymer of monomers selected from thegroup consisting of hydroxyethyl acrylate, hydroxyethyl methacrylate,hydroxypropyl acrylate, and hydroxypropyl methacrylate, and (2)methacrylic anhydride.
 23. A process in accordance with claim 1 in whichsaid crosslinkable non-water-soluble polymer is a reaction product of(1) a polymer of monomers comprising hydroxyethyl methacrylate and (2)methacrylic anhydride.
 24. A process in accordance with claim 15 inwhich said sites are thiol groups and said functionalizing agent is amember selected from the group consisting of haloacetyls, acid halides,alkyl halides, maleimides, aziridines, acrylating agents, pyridyldisulfides, disulfide reductants, and 5-thio-2-nitrobenzoic acid.
 25. Aprocess in accordance with claim 1 in which said crosslinkablenon-water-soluble polymer is a product of a reaction between (1) apolymer of monomers selected from the group consisting of3-(2,4,6-tribromo-3-methylphenoxy)-2-hydroxypropyl (meth)acrylate,3-(2,4-dibromo-3-methylphenoxy)-2-hydroxypropyl (meth)acrylate,3-(3-methyl-5-bromophenoxy)-2-hydroxypropyl (meth)acrylate,2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxyethoxy-3,5-dibromophenyl)propane,2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxy-3,5-dibromophenyl)propane,and2-(4-hydroxydiethoxy-3,5-dibromophenyl)-2-(4-methacryloxydiethoxy-3,5-dibromophenyl)propane,and (2) a functionalizing agent selected from the group consisting ofepoxides, oxiranes, carbonyldiimidazoles, periodates, acid halides,alkyl halides, isocyanates, halohydrins, and anhydrides.
 26. A processin accordance with claim 1 in which said crosslinkable non-water-solublepolymer is a product of a coupling reaction between (1) a copolymer ofhydroxyethyl methacrylate and a member selected from the groupconsisting of methacrylic acid, acrylic acid, N-vinyl pyrrolidone,dimethyl acrylamide, and vinyl alcohol, and (2) a functionalizing agentthat when coupled to said copolymer is capable of undergoing acrosslinking reaction.
 27. A process in accordance with claim 1 in whichsaid crosslinkable non-water-soluble polymer is a product of a couplingreaction between (1) a copolymer of hydroxyethyl methacrylate andmethacrylic acid, and (2) a methacrylic anhydride.
 28. A process inaccordance with claim 1 in which said non-aqueous diluent is a memberselected from the group consisting of polyethylene glycol andmonomethoxy, dimethoxy, monoethoxy, and diethoxy ethers of polyethyleneglycol, polypropylene glycol and monomethoxy, dimethoxy, monoethoxy, anddiethoxy ethers of polypropylene glycol, polybutylene glycol andmonomethoxy, dimethoxy, monoethoxy, and diethoxy ethers of polybutyleneglycol, polyglycerol and monomethoxy, dimethoxy, monoethoxy, anddiethoxy ethers of polyglycerol, and alkylated glucosides.
 29. A processin accordance with claim 1 in which said non-aqueous diluent is a memberselected from the group consisting of polyethylene glycol, polypropyleneglycol, polybutylene glycol, polyglycerol, and alkylated glucosides. 30.A process in accordance with claim 1 in which said non-aqueous diluentis polyethylene glycol.
 31. A process for the manufacture of a moldedhydrogel article, said process comprising: (a) effecting polymerizationof a monomer to form a non-water-soluble polymer which when crosslinkedand saturated with water forms a hydrogel containing a predeterminedvolumetric proportion of water, said monomer having a reactive groupthat, subsequent to polymerization of said monomer, is capable ofcoupling to a functionalizing agent defined as an agent that whencoupled to said reactive group is capable of undergoing a crosslinkingreaction; (b) contacting said non-water-soluble polymer with afunctionalizing agent as defined above to convert said non-water solublepolymer to a crosslinkable non-water soluble polymer; (c) casting acomposition comprising: (i) said crosslinkable non-water soluble polymerand (ii) a non-aqueous diluent that is inert to said crosslinkingreaction, said non-aqueous diluent being in a volumetric proportionsubstantially equal to said volumetric proportion of water in saidhydrogel, in a mold under conditions that cause said crosslinkingreaction to occur and that convert said composition to a non-aqueousgel; and (d) substituting an aqueous liquid for said non-aqueous diluentto convert said non-aqueous gel to a hydrogel.
 32. A process inaccordance with claim 31 in which said aqueous liquid is an aqueousphysiological saline solution.
 33. A process in accordance with claim 31in which step (b) comprises contacting said liquid prepolymer mixturewith an amount of said functionalizing agent selected to cause couplingof said functionalizing agent to from about 0.2% to about 5% of saidreactive groups.
 34. A process in accordance with claim 31 in which saidreactive group is a member selected from the group consisting ofhydroxyl, amino, carboxylate, thiol, disulfide, anhydride, urethane, andepoxide groups.
 35. A process in accordance with claim 31 in which saidreactive group is a hydroxyl group.
 36. A process in accordance withclaim 31 in which said monomer is a monomer or monomer mixture thatpolymerizes to a member selected from the group consisting ofpoly(hydroxyethyl acrylate), poly(hydroxyethyl methacrylate),poly(hydroxypropyl acrylate), poly(hydroxypropyl methacrylate),polyethylene glycol, cellulose, dextran, polyvinyl alcohol, poly(vinylacetate-co-vinyl alcohol), polyethylene-co-vinyl alcohol, andpolybisphenol A.
 37. A process in accordance with claim 31 in which saidmonomer is a member selected from the group consisting of hydroxyethylacrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, andhydroxypropyl methacrylate.
 38. A process in accordance with claim 31 inwhich said monomer is hydroxyethyl methacrylate.
 39. A process inaccordance with claim 31 in which said monomer is a mixture ofhydroxyethyl methacrylate, blue hydroxyethyl methacrylate, andmethacrylic acid.
 40. A process in accordance with claim 31 in whichsaid reactive group is a hydroxyl group and said functionalizing agentis a member selected from the group consisting of epoxides, oxiranes,carbonyldiimidazoles, periodates, acid halides, alkyl halides,isocyanates, halohydrins, and anhydrides.
 41. A process in accordancewith claim 31 in which said reactive group is a hydroxyl group and saidfunctionalizing agent is an anhydride.
 42. A process in accordance withclaim 31 in which said monomer is hydroxyethyl methacrylate and saidfunctionalizing agent is methacrylic anhydride.
 43. A process inaccordance with claim 31 in which said reactive group is a thiol groupand said functionalizing agent is a member selected from the groupconsisting of haloacetyls, acid halides, alkyl halides, maleimides,aziridines, acryloylsacrylating agents, pyridyl disulfides, disulfidereductants, and 5-thio-2-nitrobenzoic acid.
 44. A process in accordancewith claim 31 in which said monomer is a member selected from the groupconsisting of 3-(2,4,6-tribromo-3-methylphenoxy)-2-hydroxypropyl(meth)acrylate, 3-(2,4-dibromo-3-methylphenoxy)-2-hydroxypropyl(meth)acrylate, 3-(3-methyl-5-bromophenoxy)-2-hydroxypropyl(meth)acrylate,2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxyethoxy-3,5-dibromophenyl)propane,2-(4-hydroxyethoxy-3,5-dibromophenyl)-2-(4-acryloxy-3,5-dibromophenyl)propane,and2-(4-hydroxydiethoxy-3,5-dibromophenyl)-2-(4-methacryloxydiethoxy-3,5-dibromophenyl)propane,and said functionalizing agent is a member selected from the groupconsisting of epoxides, oxiranes, carbonyldiimidazoles, periodates, acidhalides, alkyl halides, isocyanates, halohydrins, and anhydrides.
 45. Aprocess in accordance with claim 31 in which said monomer ishydroxyethyl methacrylate and step (a) is performed in the presence of aco-monomer selected from the group consisting of methacrylic acid,acrylic acid, N-vinyl pyrrolidone, dimethyl acrylamide, and vinylalcohol, and said non-water-soluble precursor polymer is a copolymer.46. A process in accordance with claim 45 in which said co-monomer ismethacrylic acid.
 47. A process in accordance with claim 31 in whichsaid monomer is hydroxyethyl methacrylate and step (a) is performed inthe presence of co-monomers blue hydroxyethyl methacrylate andmethacrylic acid.
 48. A process in accordance with claim 31 in whichsaid non-aqueous diluent is a member selected from the group consistingof polyethylene glycol and monomethoxy, dimethoxy, monoethoxy, anddiethoxy ethers of polyethylene glycol, polypropylene glycol andmonomethoxy, dimethoxy, monoethoxy, and diethoxy ethers of polypropyleneglycol, polybutylene glycol and monomethoxy, dimethoxy, monoethoxy, anddiethoxy ethers of polybutylene glycol, polyglycerol and monomethoxy,dimethoxy, monoethoxy, and diethoxy ethers of polyglycerol, andalkylated glucosides.
 49. A process in accordance with claim 31 in whichin which said non-aqueous diluent is a member selected from the groupconsisting of polyethylene glycol, polypropylene glycol, polybutyleneglycol, polyglycerol, and alkylated glucosides.
 50. A process inaccordance with claim 31 in which in which said non-aqueous diluent ispolyethylene glycol.
 51. A process in accordance with claim 31 in whichstep (a) comprises exposing said monomer to an elevated temperature inthe presence of a thermal polymerization initiator.
 52. A process inaccordance with claim 51 in which said thermal polymerization initiatoris a member selected from the group consisting of lauryl peroxide,benzoyl peroxide, dicumyl peroxide, t-butyl hydroperoxide,azobisisobutyronitrile, potassium persulfate, and ammonium persulfate.53. A process in accordance with claim 31 in which step (c) comprisesexposing said composition to light in the presence of a photoinitiator.54. A process in accordance with claim 53 in which said photoinitiatoris a member selected from the group consisting of benzoin methyl ether,1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenylpropane-1-one, 4,4′-azobis(4-cyanovalericacid), and bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphineoxide.
 55. A process in accordance with claim 31 in which saidnon-water-soluble precursor polymer has a molecular weight of from about10,000 to about 1,000,000.
 56. A process in accordance with claim 31 inwhich said non-water-soluble precursor polymer has a molecular weight offrom about 10,000 to about 300,000.
 57. A process in accordance withclaim 31 in which said non-water-soluble precursor polymer has amolecular weight of from about 50,000 to about 150,000.
 58. Acomposition that is curable to a non-aqueous gel, said compositioncomprising a crosslinkable non-water-soluble polymer dissolved in anon-aqueous diluent to form a semi-solid, said crosslinkable polymerbearing functional groups that are capable of crosslinking saidcrosslinkable polymer in a crosslinking reaction to which saidnon-aqueous diluent is inert.
 59. A composition in accordance with claim58 in which said crosslinkable polymer is a polymer obtained by reactionof a hydroxyl-substituted precursor polymer selected from the groupconsisting of poly(hydroxyethyl acrylate), poly(hydroxyethylmethacrylate), poly(hydroxypropyl acrylate), poly(hydroxypropylmethacrylate), polyethylene glycol, cellulose, dextran, polyvinylalcohol, poly(vinyl acetate-co-vinyl alcohol), polyethylene-co-vinylalcohol, and polybisphenol A, with a member selected from the groupconsisting of epoxides, oxiranes, carbonyldiimidazoles, periodates, acidhalides, alkyl halides, isocyanates, halohydrins, and anhydrides.
 60. Acomposition in accordance with claim 58 in which said crosslinkablepolymer is a polymer obtained by reaction of a hydroxyl-substitutedprecursor polymer selected from the group consisting ofpoly(hydroxyethyl acrylate), poly(hydroxyethyl methacrylate),poly(hydroxypropyl acrylate), and poly(hydroxypropyl methacrylate) withan anhydride.
 61. A composition in accordance with claim 58 in whichsaid crosslinkable polymer is a polymer of monomers comprisinghydroxyethyl methacrylate functionalized by reaction with methacrylicanhydride.
 62. A composition in accordance with claim 58 in which saidcrosslinkable polymer is a copolymer of monomers comprising hydroxyethylmethacrylate and methacrylic acid functionalized by reaction withmethacrylic anhydride.
 63. A composition in accordance with claim 58 inwhich said crosslinkable polymer is a copolymer of hydroxyethylmethacrylate, blue hydroxyethyl methacrylate, and methacrylic acid,functionalized by reaction with methacrylic anhydride.
 64. A compositionin accordance with claim 58 further comprising a dead polymer.
 65. Acomposition in accordance with claim 58 further comprising a reactiveplasticizer.
 66. A composition in accordance with claim 58 furthercomprising a dead polymer and a reactive plasticizer.
 67. A compositionin accordance with claim 61 in which from about 0.2% to about 5% of thehydroxy groups of said polymer are coupled to said functional groups.68. A composition in accordance with claim 58 in which saidcrosslinkable polymer has a molecular weight of from about 10,000 toabout 1,000,000.
 69. A composition in accordance with claim 58 in whichsaid crosslinkable polymer has a molecular weight of from about 10,000to about 300,000.
 70. A composition in accordance with claim 58 in whichsaid crosslinkable polymer has a molecular weight of from about 50,000to about 150,000.
 71. A composition in accordance with claim 58 in whichsaid non-aqueous diluent is a member selected from the group consistingof polyethylene glycol, polypropylene glycol, polybutylene glycol,polyglycerol, and alkylated glucosides.
 72. A composition in accordancewith claim 58 in which said crosslinkable polymer is a copolymer ofmonomers comprising hydroxymethyl methacrylate and methacrylic acid ofwhich from about 0.2% to about 5% of the hydroxyl groups arefunctionalized with methacrylic anhydride.
 73. A composition inaccordance with claim 58 in which said crosslinkable polymer is acopolymer of monomers comprising hydroxymethyl methacrylate andmethacrylic acid of which from about 0.2% to about 5% of the hydroxylgroups are functionalized with methacrylic anhydride and whose molecularweight is from about 50,000 to about 150,000.